{"a690ea4ac41d4782cd472f2b1ccba483pumaizi":{"DOI":"10.1038/sj.cdd.4401735","ISBN":"1350-9047 (Print)\n1350-9047 (Linking)","ISSN":"13509047","URL":"https://www.ncbi.nlm.nih.gov/pubmed/16052236","abstract":"Tumor necrosis factor (TNF) prodrugs are fusion proteins comprised of an N-terminal single-chain antibody variable fragment (scFv) targeting a TNF effector and a C-terminal TNF receptor (TNFR)1-derived inhibitor module. Introduction of matrix metalloproteinase (MMP)-2 recognition motifs between TNF and the TNFR1 fragment allowed activation by recombinant MMP-2 and MMP-expressing HT1080 cells. Processing by endogeneous MMPs required specific membrane binding of the TNF prodrug via the targeting scFv, ensuring strictly antigen-dependent activation. Interestingly, TNF bioactivity of the processed prodrug was approximately 1000-fold higher upon scFv-mediated targeting, and signaled juxtatropic cell death also to antigen-negative cells. Microscopical analyses of TNFR2 clustering and TNF receptor-associated factor 2 recruitment at contact sites to adjacent cells revealed the formation of stable TNFR complexes by target-bound, processed prodrug, resembling the increased signal capacity of natural, membrane-expressed TNF. MMP-2-sensitive TNF prodrugs represent novel cytokine-based reagents for targeted cancer therapy, which should be exploitable for MMP-overexpressing tumors.","annote":"Gerspach, J\nMuller, D\nMunkel, S\nSelchow, O\nNemeth, J\nNoack, M\nPetrul, H\nMenrad, A\nWajant, H\nPfizenmaier, K\neng\nResearch Support, Non-U.S. Gov't\nEngland\nCell Death Differ. 2006 Feb;13(2):273-84. doi: 10.1038/sj.cdd.4401735.","author":[{"family":"Gerspach","given":"J."},{"family":"Müller","given":"D."},{"family":"Münkel","given":"S."},{"family":"Selchow","given":"O."},{"family":"Nemeth","given":"J."},{"family":"Noack","given":"M."},{"family":"Petrul","given":"H."},{"family":"Menrad","given":"A."},{"family":"Wajant","given":"H."},{"family":"Pfizenmaier","given":"Klaus"}],"citation-label":"Gerspach2006","collection-editor":[],"collection-title":"","container-author":[],"container-title":"Cell Death and Differentiation","documents":[],"edition":"2005/07/30","editor":[],"event-date":{"date-parts":[["2006"]],"literal":"2006"},"event-place":"","id":"a690ea4ac41d4782cd472f2b1ccba483pumaizi","interhash":"e4e1715ccda9122c01b0b79aaecba98b","intrahash":"a690ea4ac41d4782cd472f2b1ccba483","issue":"2","issued":{"date-parts":[["2006"]],"literal":"2006"},"keyword":"2006 izi mueller pfizenmaier","misc":{"isbn":"1350-9047 (Print)\n1350-9047 (Linking)","pmid":"16052236","issn":"13509047","doi":"10.1038/sj.cdd.4401735"},"note":"","number":"2","number-of-pages":"11","page":"273--284","page-first":"273","publisher":"","publisher-place":"","status":"","title":"Restoration of membrane TNF-like activity by cell surface targeting and matrix metalloproteinase-mediated processing of a TNF prodrug","type":"article-journal","username":"pumaizi","version":"","volume":"13"},"6802412e48ded829c7e3dca52d0258bdpumaizi":{"DOI":"","ISBN":"1464-8431 (Print)$\\backslash$r1464-8431 (Linking)","ISSN":"1464-8431","URL":"http://www.ncbi.nlm.nih.gov/pubmed/16506524","abstract":"Liposomes are potent drug delivery systems that protect the drug from degradation, improve its pharmacokinetic properties, and deliver a high drug payload. Although several liposomal formulations of chemotherapeutic drugs have been approved for cancer therapy, drug delivery by these liposomes is accomplished mainly by passive means, for example, by enhanced permeability and retention. Antibodies that generate target cell-specific immunoliposomes for improved and targeted drug delivery have been extensively tested. In the past five to ten years, tremendous progress has been made to improve the efficacy of both liposomes and of antibodies. With one immunoliposomal formulation currently being manufactured in a GMP-compliant process for preclinical studies, it is envisaged that various other immunoliposomes will follow.","annote":"Kontermann, Roland E\neng\nReview\nEngland\nCurr Opin Mol Ther. 2006 Feb;8(1):39-45.","author":[{"family":"Kontermann","given":"Roland E"}],"citation-label":"Kontermann2006","collection-editor":[],"collection-title":"","container-author":[],"container-title":"Current opinion in molecular therapeutics","documents":[],"edition":"2006/03/02","editor":[],"event-date":{"date-parts":[["2006"]],"literal":"2006"},"event-place":"","id":"6802412e48ded829c7e3dca52d0258bdpumaizi","interhash":"6fab1a01fe2a2538caee29ed44fa4283","intrahash":"6802412e48ded829c7e3dca52d0258bd","issue":"1","issued":{"date-parts":[["2006"]],"literal":"2006"},"keyword":"2006 izi kontermann","misc":{"isbn":"1464-8431 (Print)$\\backslash$r1464-8431 (Linking)","pmid":"16506524","issn":"1464-8431"},"note":"","number":"1","number-of-pages":"6","page":"39--45","page-first":"39","publisher":"","publisher-place":"","status":"","title":"Immunoliposomes for cancer therapy.","type":"article-journal","username":"pumaizi","version":"","volume":"8"},"3b5688702f5b85a56e97bb0bb01ad2f0pumaizi":{"DOI":"10.1016/j.modgep.2006.03.007","ISBN":"1567-133X (Print)$\\backslash$n1567-133X (Linking)","ISSN":"1567133X","URL":"https://www.ncbi.nlm.nih.gov/pubmed/16750940","abstract":"Protein kinase D belongs to the subfamily of CaMK. In mammals, three isoforms are known. They have been linked to diverse cellular functions including regulation of cell proliferation, differentiation, apoptosis and motility as well as secretory transport from the trans-Golgi compartment to the plasma membrane. Accordingly, the mammalian PKDs show different intracellular locations, with reported dynamic redistribution, between cytosol, Golgi, plasma membranes and the nucleus, depending on the cell type and exogenous stimuli. The genome of Drosophila melanogaster harbours just one, highly conserved PKD homologue, which is expressed throughout development. PKD mRNA expression during late embryogenesis is restricted to ectodermal derivatives including those involved in cuticle secretion. In imaginal tissues, transcription appears more uniform. PKD protein is detected predominantly in the cytosol with an enrichment in lateral apodemes of late embryos as well as in larval fascicles. In secretory tissues like salivary glands, the protein is concentrated in dotted structures. A PKD-GFP transgene reveals a similar punctuate protein accumulation juxtaposed to a resident Golgi-marker. In cultured cells, transfected Drosophila PKD-GFP colocalizes with a marker of the trans-Golgi compartment like human PKD1-GFP. Similar to the mammalian homologues, Drosophila PKD may be multifunctional including a role in secretory transport in accordance with its subcellular distribution. © 2006 Elsevier B.V. All rights reserved.","annote":"","author":[{"family":"Maier","given":"Dieter"},{"family":"Hausser","given":"Angelika"},{"family":"Nagel","given":"Anja C."},{"family":"Link","given":"Gisela"},{"family":"Kugler","given":"Sabrina J."},{"family":"Wech","given":"Irmgard"},{"family":"Pfizenmaier","given":"Klaus"},{"family":"Preiss","given":"Anette"}],"citation-label":"Maier2006","collection-editor":[],"collection-title":"","container-author":[],"container-title":"Gene Expression Patterns","documents":[],"edition":"2006/06/06","editor":[],"event-date":{"date-parts":[["2006"]],"literal":"2006"},"event-place":"","id":"3b5688702f5b85a56e97bb0bb01ad2f0pumaizi","interhash":"7465caadf5cdbeceb999f846069368be","intrahash":"3b5688702f5b85a56e97bb0bb01ad2f0","issue":"8","issued":{"date-parts":[["2006"]],"literal":"2006"},"keyword":"2006 izi hausser","misc":{"isbn":"1567-133X (Print)$\\backslash$n1567-133X (Linking)","pmid":"16750940","issn":"1567133X","doi":"10.1016/j.modgep.2006.03.007"},"note":"","number":"8","number-of-pages":"7","page":"849--856","page-first":"849","publisher":"","publisher-place":"","status":"","title":"Drosophila protein kinase D is broadly expressed and a fraction localizes to the Golgi compartment","type":"article-journal","username":"pumaizi","version":"","volume":"6"},"f2fd4567a71bedb12891617cbb04f3b6pumaizi":{"DOI":"","ISBN":"","ISSN":"","URL":"http://dx.doi.org/10.1038/sj.cdd.4402051","abstract":"","annote":"","author":[{"family":"Watermann","given":"I"},{"family":"Gerspach","given":"J"},{"family":"Lehne","given":"M"},{"family":"Seufert","given":"J"},{"family":"Schneider","given":"B"},{"family":"Pfizenmaier","given":"K"},{"family":"Wajant","given":"H"}],"citation-label":"watermann2006activation","collection-editor":[],"collection-title":"","container-author":[],"container-title":"Cell Death And Differentiation","documents":[],"edition":"","editor":[],"event-date":{"date-parts":[["2006","10"]],"literal":"2006"},"event-place":"","id":"f2fd4567a71bedb12891617cbb04f3b6pumaizi","interhash":"e21c8964fd61d2d75dc8230cc635db8c","intrahash":"f2fd4567a71bedb12891617cbb04f3b6","issue":"","issued":{"date-parts":[["2006","10"]],"literal":"2006"},"keyword":"2006 izi pfizenmaier","note":"","number":"","page":"765--","page-first":"765","publisher":"Nature Publishing Group","publisher-place":"","status":"","title":"Activation of CD95L fusion protein prodrugs by tumor-associated proteases","type":"article-journal","username":"pumaizi","version":"","volume":"14"},"3713eecc20971272e3f37992f25c290dpumaizi":{"DOI":"10.1242/jcs.03104","ISBN":"0021-9533","ISSN":"0021-9533","URL":"https://journals.biologists.com/jcs/article/119/17/3613/29160/Phospho-specific-binding-of-14-3-3-proteins-to","abstract":"Phosphatidylinositol-4-kinase-IIIbeta (PI4KIIIbeta) is activated at the Golgi compartment by PKD-mediated phosphorylation. Subsequent mechanisms responsible for continuous PtdIns(4)P production at Golgi membranes and potential interaction partners of activated PI4KIIIbeta are unknown. Here we identify phosphoserine/-threonine binding 14-3-3 proteins as novel regulators of PI4KIIIbeta activity downstream of this phosphorylation. The PI4KIIIbeta-14-3-3 interaction, evident from GST pulldowns, co-immunoprecipitations and bimolecular fluorescence complementation, was augmented by phosphatase inhibition with okadaic acid. Binding of 14-3-3 proteins to PI4KIIIbeta involved the PKD phosphorylation site Ser294, evident from reduced 14-3-3 binding to a S294A PI4KIIIbeta mutant. Expression of dominant negative 14-3-3 proteins resulted in decreased PI4KIIIbeta Ser294 phosphorylation, whereas wildtype 14-3-3 proteins increased phospho-PI4KIIIbeta levels. This was because of protection of PI4KIIIbeta Ser294 phosphorylation from phosphatase-mediated dephosphorylation. The functional significance of the PI4KIIIbeta-14-3-3 interaction was evident from a reduction of PI4KIIIbeta activity upon dominant negative 14-3-3 protein expression. We propose that 14-3-3 proteins function as positive regulators of PI4KIIIbeta activity by protecting the lipid kinase from active site dephosphorylation, thereby ensuring a continuous supply of PtdIns(4)P at the Golgi compartment.","annote":"Hausser, AngelikaLink, GiselaHoene, MiriamRusso, ChiaraSelchow, OlafPfizenmaier, KlausengResearch Support, Non-U.S. Gov'tEnglandJ Cell Sci. 2006 Sep 1;119(Pt 17):3613-21. doi: 10.1242/jcs.03104. Epub 2006 Aug 15.","author":[{"family":"Hausser","given":"Angelika"},{"family":"Link","given":"Gisela"},{"family":"Hoene","given":"Miriam"},{"family":"Russo","given":"Chiara"},{"family":"Selchow","given":"Olaf"},{"family":"Pfizenmaier","given":"Klaus"}],"citation-label":"Hausser2006","collection-editor":[],"collection-title":"","container-author":[],"container-title":"Journal of Cell Science","documents":[],"edition":"2006/08/17","editor":[],"event-date":{"date-parts":[["2006"]],"literal":"2006"},"event-place":"","id":"3713eecc20971272e3f37992f25c290dpumaizi","interhash":"48827f6bc17d3864483ffeee9a882332","intrahash":"3713eecc20971272e3f37992f25c290d","issue":"17","issued":{"date-parts":[["2006"]],"literal":"2006"},"keyword":"2006 izi pfizenmaier hausser","misc":{"isbn":"0021-9533","pmid":"16912074","issn":"0021-9533","doi":"10.1242/jcs.03104"},"note":"","number":"17","number-of-pages":"8","page":"3613--3621","page-first":"3613","publisher":"","publisher-place":"","status":"","title":"Phospho-specific binding of 14-3-3 proteins to phosphatidylinositol 4-kinase III β protects from dephosphorylation and stabilizes lipid kinase activity","type":"article-journal","username":"pumaizi","version":"","volume":"119"},"442972159c54f6c345a5075c0e974a0dpumaizi":{"DOI":"10.1080/10611860600864018","ISBN":"1061-186X (Print)\n1026-7158 (Linking)","ISSN":"1061186X","URL":"https://www.ncbi.nlm.nih.gov/pubmed/17050123","abstract":"Recently, we presented a new method for the generation of single-chain Fv (scFv) immunoliposomes, which circumvents the necessity to introduce additional reactive groups in the protein. This method is based on immobilizing scFv fragments via their C-terminal hexahistidyl-tag on liposomes containing nickel-complexed dioleoyl-glycero-succinyl-nitrilotriacetic acid (Ni-NTA-DOGS) as an anchor lipid within the lipid bilayer. Here, we have extended this approach to various other scFv fragments and further demonstrate strong and selective binding of these liposomes to target cells in vitro. In order to evaluate suitability for in vivo applications, we investigated the influence of human plasma on stability and binding behaviour of scFv Ni-NTA-liposomes in vitro using scFv A5 directed against human endoglin (CD105) as a model antibody. We could show that the binding activity to target cells is rapidly lost in the presence of human plasma. Incorporation of polyethylene glycol (PEG) chains into the lipid bilayer did not protect against loss of binding capability. Further studies showed that loss of binding is mainly due to displacement of Ni-NTA-bound scFv fragments caused by plasma proteins. In conclusion, the system allows for a rapid and flexible generation of target cell specific immunoliposomes for in vitro applications but lacks stability for in vivo applications.","annote":"Ruger, RonnyMuller, DafneFahr, AlfredKontermann, Roland EengEnglandJ Drug Target. 2006 Sep;14(8):576-82. doi: 10.1080/10611860600864018 .","author":[{"family":"Rüger","given":"Ronny"},{"family":"Müller","given":"Dafne"},{"family":"Fahr","given":"Alfred"},{"family":"Kontermann","given":"Roland E."}],"citation-label":"Ruger2006","collection-editor":[],"collection-title":"","container-author":[],"container-title":"Journal of Drug Targeting","documents":[],"edition":"2006/10/20","editor":[],"event-date":{"date-parts":[["2006"]],"literal":"2006"},"event-place":"","id":"442972159c54f6c345a5075c0e974a0dpumaizi","interhash":"9e0ad99591de4b1d240dcdeda9d51ffc","intrahash":"442972159c54f6c345a5075c0e974a0d","issue":"8","issued":{"date-parts":[["2006"]],"literal":"2006"},"keyword":"2006 izi kontermann","misc":{"isbn":"1061-186X (Print)\n1026-7158 (Linking)","pmid":"17050123","issn":"1061186X","doi":"10.1080/10611860600864018"},"note":"","number":"8","number-of-pages":"6","page":"576--582","page-first":"576","publisher":"","publisher-place":"","status":"","title":"In vitro characterization of binding and stability of single-chain Fv Ni-NTA-liposomes","type":"article-journal","username":"pumaizi","version":"","volume":"14"},"9a44957870b4a88de5507fbffcd11b52pumaizi":{"DOI":"10.1038/sj.onc.1209655","ISBN":"0950-9232 (Print)$\\backslash$r0950-9232 (Linking)","ISSN":"09509232","URL":"https://www.ncbi.nlm.nih.gov/pubmed/16702954","abstract":"The transcription factor nuclear factor kappa-B (NF-kappaB) is generally regarded as an antiapoptotic factor. Accordingly, NF-kappaB activation inhibits death ligand-induced apoptosis. In contrast, ultraviolet light B (UVB)-induced apoptosis is not inhibited but even enhanced upon NF-kappaB activation by interleukin-1 (IL-1). This study was performed to identify the molecular mechanisms underlying this switch of NF-kappaB. Enhancement of UVB-induced apoptosis was always associated with increased release of tumour necrosis factor-alpha (TNF-alpha), which was dependent on NF-kappaB activation. The same was observed when UVA and cisplatin were used, which like UVB induce base modifications. In contrast, apoptosis caused by DNA strand breaks was not enhanced by IL-1, indicating that the type of DNA damage is critical for switching the effect of NF-kappaB on apoptosis. Surprisingly, activated NF-kappaB induced TNF-alpha mRNA expression in the presence of all DNA damage-inducing agents. However, in the presence of DNA strand breaks, there was no release of the TNF-alpha protein, which is so crucial for enhancing apoptosis. Together, this indicates that induction of DNA damage may have a significant impact on biological effects but it is the type of DNA damage that determines the final outcome. This may have implications for the role of NF-kappaB in carcinogenesis and for the application of NF-kappaB inhibitors in anticancer therapy.","annote":"Strozyk, EPoppelmann, BSchwarz, TKulms, DengResearch Support, Non-U.S. Gov'tEnglandOncogene. 2006 Oct 12;25(47):6239-51. doi: 10.1038/sj.onc.1209655. Epub 2006 May 15.","author":[{"family":"Strozyk","given":"E."},{"family":"Pöppelmann","given":"B."},{"family":"Schwarz","given":"T."},{"family":"Kulms","given":"D."}],"citation-label":"Strozyk2006","collection-editor":[],"collection-title":"","container-author":[],"container-title":"Oncogene","documents":[],"edition":"2006/05/17","editor":[],"event-date":{"date-parts":[["2006"]],"literal":"2006"},"event-place":"","id":"9a44957870b4a88de5507fbffcd11b52pumaizi","interhash":"cf4d9ed3f6a5bd8a86a34349508f0719","intrahash":"9a44957870b4a88de5507fbffcd11b52","issue":"47","issued":{"date-parts":[["2006"]],"literal":"2006"},"keyword":"2006 izi kulms","misc":{"isbn":"0950-9232 (Print)$\\backslash$r0950-9232 (Linking)","pmid":"16702954","issn":"09509232","doi":"10.1038/sj.onc.1209655"},"note":"","number":"47","number-of-pages":"12","page":"6239--6251","page-first":"6239","publisher":"","publisher-place":"","status":"","title":"Differential effects of NF-κB on apoptosis induced by DNA-damaging agents: The type of DNA damage determines the final outcome","type":"article-journal","username":"pumaizi","version":"","volume":"25"},"ea7ad1b4d52c672f36e360d387760a0epumaizi":{"DOI":"10.1007/s00109-006-0073-1","ISBN":"0946-2716 (Print)$\\backslash$r0946-2716 (Linking)","ISSN":"09462716","URL":"https://www.ncbi.nlm.nih.gov/pubmed/16924474","abstract":"We analyzed a novel bifunctional fusion protein, CD40ed-CD95Led, consisting amino-terminally of the extracellular domain of CD40 and carboxy-terminally of the extracellular domain of CD95L. On cells lacking CD40L, this fusion protein is poorly active with respect to CD95 activation [median effective dose (ED50)\\textgreater1 microg/ml], but it stimulates CD95 signaling with high efficiency upon binding to membrane-expressed CD40L (ED50\\textless1 ng/ml). Thus, cell surface immobilization mediated by the CD40 part of the molecule unmasks the high-latent, CD95-stimulating capacity of the otherwise poorly active CD95L fusion protein. Moreover, interaction of the CD40 part of CD40ed-CD95Led with CD40L prevents the activation of cellular CD40. The CD40ed-CD95Led fusion protein therefore simultaneously blocks antiapoptotic CD40 activation and induces CD95-mediated apoptosis. Indeed, T47D cells displaying an antiapoptotic autocrine CD40-CD40L signaling loop were significantly more sensitive toward CD40ed-CD95Led than toward soluble CD95L artificially activated by crosslinking. Fusion proteins of RANK and CD95L (RANKed-CD95Led) and CD40 and tumor necrosis factor-related apoptosis inducing ligand (TRAIL) (CD40ed-TRAILed), with domain architectures similar to CD40ed-Cd95Led, displayed RANKL-dependent CD95 and CD40L-dependent TRAILR2 activation, respectively, indicating the principle feasibility of this fusion protein design.","annote":"","author":[{"family":"Assohou-Luty","given":"Constance"},{"family":"Gerspach","given":"Jeanette"},{"family":"Siegmund","given":"Daniela"},{"family":"Müller","given":"Nicole"},{"family":"Huard","given":"Bertrand"},{"family":"Tiegs","given":"Gisa"},{"family":"Pfizenmaier","given":"Klaus"},{"family":"Wajant","given":"Harald"}],"citation-label":"Assohou-Luty2006","collection-editor":[],"collection-title":"","container-author":[],"container-title":"Journal of Molecular Medicine","documents":[],"edition":"2006/08/23","editor":[],"event-date":{"date-parts":[["2006"]],"literal":"2006"},"event-place":"","id":"ea7ad1b4d52c672f36e360d387760a0epumaizi","interhash":"b7520997ca1a6529152830ba3bae780a","intrahash":"ea7ad1b4d52c672f36e360d387760a0e","issue":"9","issued":{"date-parts":[["2006"]],"literal":"2006"},"keyword":"2006 izi pfizenmaier","misc":{"isbn":"0946-2716 (Print)$\\backslash$r0946-2716 (Linking)","pmid":"16924474","issn":"09462716","doi":"10.1007/s00109-006-0073-1"},"note":"","number":"9","number-of-pages":"12","page":"785--797","page-first":"785","publisher":"","publisher-place":"","status":"","title":"A CD40-CD95L fusion protein interferes with CD40L-induced prosurvival signaling and allows membrane CD40L-restricted activation of CD95","type":"article-journal","username":"pumaizi","version":"","volume":"84"},"299fd46a15b204ca58f6b766b2db30f6pumaizi":{"DOI":"10.1007/s00262-006-0162-6","ISBN":"0340-7004 (Print)\n0340-7004 (Linking)","ISSN":"03407004","URL":"https://www.ncbi.nlm.nih.gov/pubmed/16636812","abstract":"We have previously developed TNF prodrugs comprised of a N-terminal scFv targeting, a TNF effector and a C-terminal TNFR1-derived inhibitor module linked to TNF via a MMP-2 motif containing peptide, allowing activation by MMP-2-expressing tumor cells. To overcome the known heterogeneity of matrix metalloprotease expression, we developed TNF prodrugs that become processed by other tumor and/or stroma-associated proteases. These TNF prodrugs comprise either an uPA-selective or a dual uPA-MMP-2-specific linker which displayed efficient, target-dependent and cleavage sequence-specific activation by the corresponding tumor cell-expressed proteases. Selective pharmacologic inhibition of endogenous uPA and MMP-2 confirm independent prodrug processing by these two model proteases and indicate the functional superiority of a prodrug containing a multi-specific protease linker. Processing optimised TNF prodrugs should increase the proportion of active therapeutic within the targeted tissue and thus potentially enhance tumor response rate.","annote":"Gerspach, JeannetteNemeth, JuliaMunkel, SabineWajant, HaraldPfizenmaier, KlausengResearch Support, Non-U.S. Gov'tGermanyCancer Immunol Immunother. 2006 Dec;55(12):1590-600. doi: 10.1007/s00262-006-0162-6. Epub 2006 Apr 25.","author":[{"family":"Gerspach","given":"Jeannette"},{"family":"Németh","given":"Julia"},{"family":"Münkel","given":"Sabine"},{"family":"Wajant","given":"Harald"},{"family":"Pfizenmaier","given":"Klaus"}],"citation-label":"Gerspach2006a","collection-editor":[],"collection-title":"","container-author":[],"container-title":"Cancer Immunology, Immunotherapy","documents":[],"edition":"2006/04/26","editor":[],"event-date":{"date-parts":[["2006"]],"literal":"2006"},"event-place":"","id":"299fd46a15b204ca58f6b766b2db30f6pumaizi","interhash":"c33839b86c42507b9337232e749f9e2d","intrahash":"299fd46a15b204ca58f6b766b2db30f6","issue":"12","issued":{"date-parts":[["2006"]],"literal":"2006"},"keyword":"2006 izi pfizenmaier","misc":{"isbn":"0340-7004 (Print)\n0340-7004 (Linking)","pmid":"16636812","issn":"03407004","doi":"10.1007/s00262-006-0162-6"},"note":"","number":"12","number-of-pages":"10","page":"1590--1600","page-first":"1590","publisher":"","publisher-place":"","status":"","title":"Target-selective activation of a TNF prodrug by urokinase-type plasminogen activator (uPA) mediated proteolytic processing at the cell surface","type":"article-journal","username":"pumaizi","version":"","volume":"55"},"134c917f5abfc29280a04b582a34ab23pumaizi":{"DOI":"10.1016/S0083-6729(06)74011-0","ISBN":"0127098747","ISSN":"00836729","URL":"https://www.ncbi.nlm.nih.gov/pubmed/17027519","abstract":"Cytokines represent a heterogeneous group of soluble mediators which are involved in almost any physiological and pathological process. The release of many cytokines and numerous of their biological activities are mediated by nuclear factor-$\\kappa$B (NF-$\\kappa$B). NF-$\\kappa$B is a ubiquitous transcription factor which is crucially involved in many biological processes, including tissue development and maintenance of tissue homeostasis. NF-$\\kappa$B also controls apoptotic cell death of both normal and malignant cells. Thus, it is a challenging target for anticancer and anti-inflammatory strategies. However, it has been recognized that NF-$\\kappa$B does not only influence many biological processes but also under certain conditions the activities of NF-$\\kappa$B can be altered as well, for example, by cytokines. This cross talk needs to be taken into account when developing strategies targeting NF-$\\kappa$B for anticancer therapy. © 2006 Elsevier Inc. All rights reserved.","annote":"Kulms, DagmarSchwarz, ThomasengReviewVitam Horm. 2006;74:283-300. doi: 10.1016/S0083-6729(06)74011-0.","author":[{"family":"Kulms","given":"Dagmar"},{"family":"Schwarz","given":"Thomas"}],"citation-label":"Kulms2006","collection-editor":[],"collection-title":"","container-author":[],"container-title":"Vitamins and Hormones","documents":[],"edition":"2006/10/10","editor":[],"event-date":{"date-parts":[["2006"]],"literal":"2006"},"event-place":"","id":"134c917f5abfc29280a04b582a34ab23pumaizi","interhash":"261c988c62028a8ac7354e18f7cce8de","intrahash":"134c917f5abfc29280a04b582a34ab23","issue":"","issued":{"date-parts":[["2006"]],"literal":"2006"},"keyword":"2006 izi kulms","misc":{"isbn":"0127098747","pmid":"17027519","issn":"00836729","doi":"10.1016/S0083-6729(06)74011-0"},"note":"","number":"","number-of-pages":"17","page":"283--300","page-first":"283","publisher":"","publisher-place":"","status":"","title":"NF-κB and Cytokines","type":"article-journal","username":"pumaizi","version":"","volume":"74"},"36fc6f016737d4cbe98571a3122124cbpumaizi":{"DOI":"10.1158/0008-5472.CAN-06-0634","ISBN":"0008-5472 (Print)$\\backslash$r0008-5472 (Linking)","ISSN":"0008-5472","URL":"http://cancerres.aacrjournals.org/lookup/doi/10.1158/0008-5472.CAN-06-0634","abstract":"Transforming growth factor-beta (TGF-beta), a multifunctional growth factor, plays an important role in breast cancer. There is increasing evidence that enhanced expression of TGF-beta promotes breast cancer progression contributing to metastasis and invasiveness of the tumor. We identified a functional polymorphism in the TGFB2 promoter, a 4-bp insertion at position -246 relative to the transcriptional start site (-246ins). Transient transfection experiments showed that the -246ins polymorphism significantly increased TGFB2 promoter activity in breast cancer cells. Electrophoretic mobility shift assays revealed binding of the transcription factor Sp1 to the -246ins allele. Overexpression of Sp1 enhanced promoter activity of the -246ins allele, demonstrating that Sp1 mediates transcriptional activation. Furthermore, the -246ins allele was associated with enhanced TGF-beta(2) expression in breast cancer tissue (P = 0.0005). To evaluate the role of the polymorphism in breast cancer, frequency of the -246ins allele was determined in breast cancer patients (n = 78) and healthy female controls (n = 143). No significant differences were found. However, the presence of the -246ins allele was associated with lymph node metastasis (P = 0.003). The -246ins allele was a significant predictor for lymph node metastasis independent of estrogen and progesterone receptor status in a multivariate logistic regression analysis (P = 0.0118, odds ratio, 5.18; 95\\% confidence interval, 1.44-18.62). We provide evidence that the TGFB2 -246ins polymorphism leads to enhanced TGF-beta(2) expression levels in vivo and might thereby contribute to tumor progression and development of metastases.","annote":"","author":[{"family":"Beisner","given":"Julia"},{"family":"Buck","given":"Miriam B."},{"family":"Fritz","given":"Peter"},{"family":"Dippon","given":"Jürgen"},{"family":"Schwab","given":"Matthias"},{"family":"Brauch","given":"Hiltrud"},{"family":"Zugmaier","given":"Gerhard"},{"family":"Pfizenmaier","given":"Klaus"},{"family":"Knabbe","given":"Cornelius"}],"citation-label":"beisner2006novel","collection-editor":[],"collection-title":"","container-author":[],"container-title":"Cancer Research","documents":[],"edition":"","editor":[],"event-date":{"date-parts":[["2006","08"]],"literal":"2006"},"event-place":"","id":"36fc6f016737d4cbe98571a3122124cbpumaizi","interhash":"cc8e345d3acc0a1d27e5f036f98c07e1","intrahash":"36fc6f016737d4cbe98571a3122124cb","issue":"15","issued":{"date-parts":[["2006","08"]],"literal":"2006"},"keyword":"2006 izi pfizenmaier","misc":{"isbn":"0008-5472 (Print)$\\backslash$r0008-5472 (Linking)","issn":"0008-5472","doi":"10.1158/0008-5472.CAN-06-0634"},"note":"","number":"15","number-of-pages":"7","page":"7554--7561","page-first":"7554","publisher":"","publisher-place":"","status":"","title":"A Novel Functional Polymorphism in the Transforming Growth Factor-β2 Gene Promoter and Tumor Progression in Breast Cancer","type":"article-journal","username":"pumaizi","version":"","volume":"66"},"6802412e48ded829c7e3dca52d0258bdfabian":{"DOI":"","ISBN":"1464-8431 (Print)$\\backslash$r1464-8431 (Linking)","ISSN":"1464-8431","URL":"http://www.ncbi.nlm.nih.gov/pubmed/16506524","abstract":"Liposomes are potent drug delivery systems that protect the drug from degradation, improve its pharmacokinetic properties, and deliver a high drug payload. Although several liposomal formulations of chemotherapeutic drugs have been approved for cancer therapy, drug delivery by these liposomes is accomplished mainly by passive means, for example, by enhanced permeability and retention. Antibodies that generate target cell-specific immunoliposomes for improved and targeted drug delivery have been extensively tested. In the past five to ten years, tremendous progress has been made to improve the efficacy of both liposomes and of antibodies. With one immunoliposomal formulation currently being manufactured in a GMP-compliant process for preclinical studies, it is envisaged that various other immunoliposomes will follow.","annote":"Kontermann, Roland E\neng\nReview\nEngland\nCurr Opin Mol Ther. 2006 Feb;8(1):39-45.","author":[{"family":"Kontermann","given":"Roland E"}],"citation-label":"Kontermann2006","collection-editor":[],"collection-title":"","container-author":[],"container-title":"Current opinion in molecular therapeutics","documents":[],"edition":"2006/03/02","editor":[],"event-date":{"date-parts":[["2006"]],"literal":"2006"},"event-place":"","id":"6802412e48ded829c7e3dca52d0258bdfabian","interhash":"6fab1a01fe2a2538caee29ed44fa4283","intrahash":"6802412e48ded829c7e3dca52d0258bd","issue":"1","issued":{"date-parts":[["2006"]],"literal":"2006"},"keyword":"2006 izi kontermann","misc":{"isbn":"1464-8431 (Print)$\\backslash$r1464-8431 (Linking)","pmid":"16506524","issn":"1464-8431"},"note":"","number":"1","number-of-pages":"6","page":"39--45","page-first":"39","publisher":"","publisher-place":"","status":"","title":"Immunoliposomes for cancer therapy.","type":"article-journal","username":"fabian","version":"","volume":"8"},"442972159c54f6c345a5075c0e974a0dfabian":{"DOI":"10.1080/10611860600864018","ISBN":"1061-186X (Print)\n1026-7158 (Linking)","ISSN":"1061186X","URL":"https://www.ncbi.nlm.nih.gov/pubmed/17050123","abstract":"Recently, we presented a new method for the generation of single-chain Fv (scFv) immunoliposomes, which circumvents the necessity to introduce additional reactive groups in the protein. This method is based on immobilizing scFv fragments via their C-terminal hexahistidyl-tag on liposomes containing nickel-complexed dioleoyl-glycero-succinyl-nitrilotriacetic acid (Ni-NTA-DOGS) as an anchor lipid within the lipid bilayer. Here, we have extended this approach to various other scFv fragments and further demonstrate strong and selective binding of these liposomes to target cells in vitro. In order to evaluate suitability for in vivo applications, we investigated the influence of human plasma on stability and binding behaviour of scFv Ni-NTA-liposomes in vitro using scFv A5 directed against human endoglin (CD105) as a model antibody. We could show that the binding activity to target cells is rapidly lost in the presence of human plasma. Incorporation of polyethylene glycol (PEG) chains into the lipid bilayer did not protect against loss of binding capability. Further studies showed that loss of binding is mainly due to displacement of Ni-NTA-bound scFv fragments caused by plasma proteins. In conclusion, the system allows for a rapid and flexible generation of target cell specific immunoliposomes for in vitro applications but lacks stability for in vivo applications.","annote":"Ruger, RonnyMuller, DafneFahr, AlfredKontermann, Roland EengEnglandJ Drug Target. 2006 Sep;14(8):576-82. doi: 10.1080/10611860600864018 .","author":[{"family":"Rüger","given":"Ronny"},{"family":"Müller","given":"Dafne"},{"family":"Fahr","given":"Alfred"},{"family":"Kontermann","given":"Roland E."}],"citation-label":"Ruger2006","collection-editor":[],"collection-title":"","container-author":[],"container-title":"Journal of Drug Targeting","documents":[],"edition":"2006/10/20","editor":[],"event-date":{"date-parts":[["2006"]],"literal":"2006"},"event-place":"","id":"442972159c54f6c345a5075c0e974a0dfabian","interhash":"9e0ad99591de4b1d240dcdeda9d51ffc","intrahash":"442972159c54f6c345a5075c0e974a0d","issue":"8","issued":{"date-parts":[["2006"]],"literal":"2006"},"keyword":"2006 izi kontermann","misc":{"isbn":"1061-186X (Print)\n1026-7158 (Linking)","pmid":"17050123","issn":"1061186X","doi":"10.1080/10611860600864018"},"note":"","number":"8","number-of-pages":"6","page":"576--582","page-first":"576","publisher":"","publisher-place":"","status":"","title":"In vitro characterization of binding and stability of single-chain Fv Ni-NTA-liposomes","type":"article-journal","username":"fabian","version":"","volume":"14"},"36fc6f016737d4cbe98571a3122124cbfabian":{"DOI":"10.1158/0008-5472.CAN-06-0634","ISBN":"0008-5472 (Print)$\\backslash$r0008-5472 (Linking)","ISSN":"0008-5472","URL":"http://cancerres.aacrjournals.org/lookup/doi/10.1158/0008-5472.CAN-06-0634","abstract":"Transforming growth factor-beta (TGF-beta), a multifunctional growth factor, plays an important role in breast cancer. There is increasing evidence that enhanced expression of TGF-beta promotes breast cancer progression contributing to metastasis and invasiveness of the tumor. We identified a functional polymorphism in the TGFB2 promoter, a 4-bp insertion at position -246 relative to the transcriptional start site (-246ins). Transient transfection experiments showed that the -246ins polymorphism significantly increased TGFB2 promoter activity in breast cancer cells. Electrophoretic mobility shift assays revealed binding of the transcription factor Sp1 to the -246ins allele. Overexpression of Sp1 enhanced promoter activity of the -246ins allele, demonstrating that Sp1 mediates transcriptional activation. Furthermore, the -246ins allele was associated with enhanced TGF-beta(2) expression in breast cancer tissue (P = 0.0005). To evaluate the role of the polymorphism in breast cancer, frequency of the -246ins allele was determined in breast cancer patients (n = 78) and healthy female controls (n = 143). No significant differences were found. However, the presence of the -246ins allele was associated with lymph node metastasis (P = 0.003). The -246ins allele was a significant predictor for lymph node metastasis independent of estrogen and progesterone receptor status in a multivariate logistic regression analysis (P = 0.0118, odds ratio, 5.18; 95\\% confidence interval, 1.44-18.62). We provide evidence that the TGFB2 -246ins polymorphism leads to enhanced TGF-beta(2) expression levels in vivo and might thereby contribute to tumor progression and development of metastases.","annote":"","author":[{"family":"Beisner","given":"Julia"},{"family":"Buck","given":"Miriam B."},{"family":"Fritz","given":"Peter"},{"family":"Dippon","given":"Jürgen"},{"family":"Schwab","given":"Matthias"},{"family":"Brauch","given":"Hiltrud"},{"family":"Zugmaier","given":"Gerhard"},{"family":"Pfizenmaier","given":"Klaus"},{"family":"Knabbe","given":"Cornelius"}],"citation-label":"beisner2006novel","collection-editor":[],"collection-title":"","container-author":[],"container-title":"Cancer Research","documents":[],"edition":"","editor":[],"event-date":{"date-parts":[["2006","08"]],"literal":"2006"},"event-place":"","id":"36fc6f016737d4cbe98571a3122124cbfabian","interhash":"cc8e345d3acc0a1d27e5f036f98c07e1","intrahash":"36fc6f016737d4cbe98571a3122124cb","issue":"15","issued":{"date-parts":[["2006","08"]],"literal":"2006"},"keyword":"2006 izi pfizenmaier","misc":{"isbn":"0008-5472 (Print)$\\backslash$r0008-5472 (Linking)","issn":"0008-5472","doi":"10.1158/0008-5472.CAN-06-0634"},"note":"","number":"15","number-of-pages":"7","page":"7554--7561","page-first":"7554","publisher":"","publisher-place":"","status":"","title":"A Novel Functional Polymorphism in the Transforming Growth Factor-β2 Gene Promoter and Tumor Progression in Breast Cancer","type":"article-journal","username":"fabian","version":"","volume":"66"},"9a44957870b4a88de5507fbffcd11b52fabian":{"DOI":"10.1038/sj.onc.1209655","ISBN":"0950-9232 (Print)$\\backslash$r0950-9232 (Linking)","ISSN":"09509232","URL":"https://www.ncbi.nlm.nih.gov/pubmed/16702954","abstract":"The transcription factor nuclear factor kappa-B (NF-kappaB) is generally regarded as an antiapoptotic factor. Accordingly, NF-kappaB activation inhibits death ligand-induced apoptosis. In contrast, ultraviolet light B (UVB)-induced apoptosis is not inhibited but even enhanced upon NF-kappaB activation by interleukin-1 (IL-1). This study was performed to identify the molecular mechanisms underlying this switch of NF-kappaB. Enhancement of UVB-induced apoptosis was always associated with increased release of tumour necrosis factor-alpha (TNF-alpha), which was dependent on NF-kappaB activation. The same was observed when UVA and cisplatin were used, which like UVB induce base modifications. In contrast, apoptosis caused by DNA strand breaks was not enhanced by IL-1, indicating that the type of DNA damage is critical for switching the effect of NF-kappaB on apoptosis. Surprisingly, activated NF-kappaB induced TNF-alpha mRNA expression in the presence of all DNA damage-inducing agents. However, in the presence of DNA strand breaks, there was no release of the TNF-alpha protein, which is so crucial for enhancing apoptosis. Together, this indicates that induction of DNA damage may have a significant impact on biological effects but it is the type of DNA damage that determines the final outcome. This may have implications for the role of NF-kappaB in carcinogenesis and for the application of NF-kappaB inhibitors in anticancer therapy.","annote":"Strozyk, EPoppelmann, BSchwarz, TKulms, DengResearch Support, Non-U.S. Gov'tEnglandOncogene. 2006 Oct 12;25(47):6239-51. doi: 10.1038/sj.onc.1209655. Epub 2006 May 15.","author":[{"family":"Strozyk","given":"E."},{"family":"Pöppelmann","given":"B."},{"family":"Schwarz","given":"T."},{"family":"Kulms","given":"D."}],"citation-label":"Strozyk2006","collection-editor":[],"collection-title":"","container-author":[],"container-title":"Oncogene","documents":[],"edition":"2006/05/17","editor":[],"event-date":{"date-parts":[["2006"]],"literal":"2006"},"event-place":"","id":"9a44957870b4a88de5507fbffcd11b52fabian","interhash":"cf4d9ed3f6a5bd8a86a34349508f0719","intrahash":"9a44957870b4a88de5507fbffcd11b52","issue":"47","issued":{"date-parts":[["2006"]],"literal":"2006"},"keyword":"2006 izi kulms","misc":{"isbn":"0950-9232 (Print)$\\backslash$r0950-9232 (Linking)","pmid":"16702954","issn":"09509232","doi":"10.1038/sj.onc.1209655"},"note":"","number":"47","number-of-pages":"12","page":"6239--6251","page-first":"6239","publisher":"","publisher-place":"","status":"","title":"Differential effects of NF-κB on apoptosis induced by DNA-damaging agents: The type of DNA damage determines the final outcome","type":"article-journal","username":"fabian","version":"","volume":"25"},"299fd46a15b204ca58f6b766b2db30f6fabian":{"DOI":"10.1007/s00262-006-0162-6","ISBN":"0340-7004 (Print)\n0340-7004 (Linking)","ISSN":"03407004","URL":"https://www.ncbi.nlm.nih.gov/pubmed/16636812","abstract":"We have previously developed TNF prodrugs comprised of a N-terminal scFv targeting, a TNF effector and a C-terminal TNFR1-derived inhibitor module linked to TNF via a MMP-2 motif containing peptide, allowing activation by MMP-2-expressing tumor cells. To overcome the known heterogeneity of matrix metalloprotease expression, we developed TNF prodrugs that become processed by other tumor and/or stroma-associated proteases. These TNF prodrugs comprise either an uPA-selective or a dual uPA-MMP-2-specific linker which displayed efficient, target-dependent and cleavage sequence-specific activation by the corresponding tumor cell-expressed proteases. Selective pharmacologic inhibition of endogenous uPA and MMP-2 confirm independent prodrug processing by these two model proteases and indicate the functional superiority of a prodrug containing a multi-specific protease linker. Processing optimised TNF prodrugs should increase the proportion of active therapeutic within the targeted tissue and thus potentially enhance tumor response rate.","annote":"Gerspach, JeannetteNemeth, JuliaMunkel, SabineWajant, HaraldPfizenmaier, KlausengResearch Support, Non-U.S. Gov'tGermanyCancer Immunol Immunother. 2006 Dec;55(12):1590-600. doi: 10.1007/s00262-006-0162-6. Epub 2006 Apr 25.","author":[{"family":"Gerspach","given":"Jeannette"},{"family":"Németh","given":"Julia"},{"family":"Münkel","given":"Sabine"},{"family":"Wajant","given":"Harald"},{"family":"Pfizenmaier","given":"Klaus"}],"citation-label":"Gerspach2006a","collection-editor":[],"collection-title":"","container-author":[],"container-title":"Cancer Immunology, Immunotherapy","documents":[],"edition":"2006/04/26","editor":[],"event-date":{"date-parts":[["2006"]],"literal":"2006"},"event-place":"","id":"299fd46a15b204ca58f6b766b2db30f6fabian","interhash":"c33839b86c42507b9337232e749f9e2d","intrahash":"299fd46a15b204ca58f6b766b2db30f6","issue":"12","issued":{"date-parts":[["2006"]],"literal":"2006"},"keyword":"2006 izi pfizenmaier","misc":{"isbn":"0340-7004 (Print)\n0340-7004 (Linking)","pmid":"16636812","issn":"03407004","doi":"10.1007/s00262-006-0162-6"},"note":"","number":"12","number-of-pages":"10","page":"1590--1600","page-first":"1590","publisher":"","publisher-place":"","status":"","title":"Target-selective activation of a TNF prodrug by urokinase-type plasminogen activator (uPA) mediated proteolytic processing at the cell surface","type":"article-journal","username":"fabian","version":"","volume":"55"},"3b5688702f5b85a56e97bb0bb01ad2f0fabian":{"DOI":"10.1016/j.modgep.2006.03.007","ISBN":"1567-133X (Print)$\\backslash$n1567-133X (Linking)","ISSN":"1567133X","URL":"https://www.ncbi.nlm.nih.gov/pubmed/16750940","abstract":"Protein kinase D belongs to the subfamily of CaMK. In mammals, three isoforms are known. They have been linked to diverse cellular functions including regulation of cell proliferation, differentiation, apoptosis and motility as well as secretory transport from the trans-Golgi compartment to the plasma membrane. Accordingly, the mammalian PKDs show different intracellular locations, with reported dynamic redistribution, between cytosol, Golgi, plasma membranes and the nucleus, depending on the cell type and exogenous stimuli. The genome of Drosophila melanogaster harbours just one, highly conserved PKD homologue, which is expressed throughout development. PKD mRNA expression during late embryogenesis is restricted to ectodermal derivatives including those involved in cuticle secretion. In imaginal tissues, transcription appears more uniform. PKD protein is detected predominantly in the cytosol with an enrichment in lateral apodemes of late embryos as well as in larval fascicles. In secretory tissues like salivary glands, the protein is concentrated in dotted structures. A PKD-GFP transgene reveals a similar punctuate protein accumulation juxtaposed to a resident Golgi-marker. In cultured cells, transfected Drosophila PKD-GFP colocalizes with a marker of the trans-Golgi compartment like human PKD1-GFP. Similar to the mammalian homologues, Drosophila PKD may be multifunctional including a role in secretory transport in accordance with its subcellular distribution. © 2006 Elsevier B.V. All rights reserved.","annote":"","author":[{"family":"Maier","given":"Dieter"},{"family":"Hausser","given":"Angelika"},{"family":"Nagel","given":"Anja C."},{"family":"Link","given":"Gisela"},{"family":"Kugler","given":"Sabrina J."},{"family":"Wech","given":"Irmgard"},{"family":"Pfizenmaier","given":"Klaus"},{"family":"Preiss","given":"Anette"}],"citation-label":"Maier2006","collection-editor":[],"collection-title":"","container-author":[],"container-title":"Gene Expression Patterns","documents":[],"edition":"2006/06/06","editor":[],"event-date":{"date-parts":[["2006"]],"literal":"2006"},"event-place":"","id":"3b5688702f5b85a56e97bb0bb01ad2f0fabian","interhash":"7465caadf5cdbeceb999f846069368be","intrahash":"3b5688702f5b85a56e97bb0bb01ad2f0","issue":"8","issued":{"date-parts":[["2006"]],"literal":"2006"},"keyword":"2006 izi hausser","misc":{"isbn":"1567-133X (Print)$\\backslash$n1567-133X (Linking)","pmid":"16750940","issn":"1567133X","doi":"10.1016/j.modgep.2006.03.007"},"note":"","number":"8","number-of-pages":"7","page":"849--856","page-first":"849","publisher":"","publisher-place":"","status":"","title":"Drosophila protein kinase D is broadly expressed and a fraction localizes to the Golgi compartment","type":"article-journal","username":"fabian","version":"","volume":"6"},"3713eecc20971272e3f37992f25c290dfabian":{"DOI":"10.1242/jcs.03104","ISBN":"0021-9533","ISSN":"0021-9533","URL":"https://journals.biologists.com/jcs/article/119/17/3613/29160/Phospho-specific-binding-of-14-3-3-proteins-to","abstract":"Phosphatidylinositol-4-kinase-IIIbeta (PI4KIIIbeta) is activated at the Golgi compartment by PKD-mediated phosphorylation. Subsequent mechanisms responsible for continuous PtdIns(4)P production at Golgi membranes and potential interaction partners of activated PI4KIIIbeta are unknown. Here we identify phosphoserine/-threonine binding 14-3-3 proteins as novel regulators of PI4KIIIbeta activity downstream of this phosphorylation. The PI4KIIIbeta-14-3-3 interaction, evident from GST pulldowns, co-immunoprecipitations and bimolecular fluorescence complementation, was augmented by phosphatase inhibition with okadaic acid. Binding of 14-3-3 proteins to PI4KIIIbeta involved the PKD phosphorylation site Ser294, evident from reduced 14-3-3 binding to a S294A PI4KIIIbeta mutant. Expression of dominant negative 14-3-3 proteins resulted in decreased PI4KIIIbeta Ser294 phosphorylation, whereas wildtype 14-3-3 proteins increased phospho-PI4KIIIbeta levels. This was because of protection of PI4KIIIbeta Ser294 phosphorylation from phosphatase-mediated dephosphorylation. The functional significance of the PI4KIIIbeta-14-3-3 interaction was evident from a reduction of PI4KIIIbeta activity upon dominant negative 14-3-3 protein expression. We propose that 14-3-3 proteins function as positive regulators of PI4KIIIbeta activity by protecting the lipid kinase from active site dephosphorylation, thereby ensuring a continuous supply of PtdIns(4)P at the Golgi compartment.","annote":"Hausser, AngelikaLink, GiselaHoene, MiriamRusso, ChiaraSelchow, OlafPfizenmaier, KlausengResearch Support, Non-U.S. Gov'tEnglandJ Cell Sci. 2006 Sep 1;119(Pt 17):3613-21. doi: 10.1242/jcs.03104. Epub 2006 Aug 15.","author":[{"family":"Hausser","given":"Angelika"},{"family":"Link","given":"Gisela"},{"family":"Hoene","given":"Miriam"},{"family":"Russo","given":"Chiara"},{"family":"Selchow","given":"Olaf"},{"family":"Pfizenmaier","given":"Klaus"}],"citation-label":"Hausser2006","collection-editor":[],"collection-title":"","container-author":[],"container-title":"Journal of Cell Science","documents":[],"edition":"2006/08/17","editor":[],"event-date":{"date-parts":[["2006"]],"literal":"2006"},"event-place":"","id":"3713eecc20971272e3f37992f25c290dfabian","interhash":"48827f6bc17d3864483ffeee9a882332","intrahash":"3713eecc20971272e3f37992f25c290d","issue":"17","issued":{"date-parts":[["2006"]],"literal":"2006"},"keyword":"2006 izi pfizenmaier hausser","misc":{"isbn":"0021-9533","pmid":"16912074","issn":"0021-9533","doi":"10.1242/jcs.03104"},"note":"","number":"17","number-of-pages":"8","page":"3613--3621","page-first":"3613","publisher":"","publisher-place":"","status":"","title":"Phospho-specific binding of 14-3-3 proteins to phosphatidylinositol 4-kinase III β protects from dephosphorylation and stabilizes lipid kinase activity","type":"article-journal","username":"fabian","version":"","volume":"119"},"134c917f5abfc29280a04b582a34ab23fabian":{"DOI":"10.1016/S0083-6729(06)74011-0","ISBN":"0127098747","ISSN":"00836729","URL":"https://www.ncbi.nlm.nih.gov/pubmed/17027519","abstract":"Cytokines represent a heterogeneous group of soluble mediators which are involved in almost any physiological and pathological process. The release of many cytokines and numerous of their biological activities are mediated by nuclear factor-$\\kappa$B (NF-$\\kappa$B). NF-$\\kappa$B is a ubiquitous transcription factor which is crucially involved in many biological processes, including tissue development and maintenance of tissue homeostasis. NF-$\\kappa$B also controls apoptotic cell death of both normal and malignant cells. Thus, it is a challenging target for anticancer and anti-inflammatory strategies. However, it has been recognized that NF-$\\kappa$B does not only influence many biological processes but also under certain conditions the activities of NF-$\\kappa$B can be altered as well, for example, by cytokines. This cross talk needs to be taken into account when developing strategies targeting NF-$\\kappa$B for anticancer therapy. © 2006 Elsevier Inc. All rights reserved.","annote":"Kulms, DagmarSchwarz, ThomasengReviewVitam Horm. 2006;74:283-300. doi: 10.1016/S0083-6729(06)74011-0.","author":[{"family":"Kulms","given":"Dagmar"},{"family":"Schwarz","given":"Thomas"}],"citation-label":"Kulms2006","collection-editor":[],"collection-title":"","container-author":[],"container-title":"Vitamins and Hormones","documents":[],"edition":"2006/10/10","editor":[],"event-date":{"date-parts":[["2006"]],"literal":"2006"},"event-place":"","id":"134c917f5abfc29280a04b582a34ab23fabian","interhash":"261c988c62028a8ac7354e18f7cce8de","intrahash":"134c917f5abfc29280a04b582a34ab23","issue":"","issued":{"date-parts":[["2006"]],"literal":"2006"},"keyword":"2006 izi kulms","misc":{"isbn":"0127098747","pmid":"17027519","issn":"00836729","doi":"10.1016/S0083-6729(06)74011-0"},"note":"","number":"","number-of-pages":"17","page":"283--300","page-first":"283","publisher":"","publisher-place":"","status":"","title":"NF-κB and Cytokines","type":"article-journal","username":"fabian","version":"","volume":"74"},"ea7ad1b4d52c672f36e360d387760a0efabian":{"DOI":"10.1007/s00109-006-0073-1","ISBN":"0946-2716 (Print)$\\backslash$r0946-2716 (Linking)","ISSN":"09462716","URL":"https://www.ncbi.nlm.nih.gov/pubmed/16924474","abstract":"We analyzed a novel bifunctional fusion protein, CD40ed-CD95Led, consisting amino-terminally of the extracellular domain of CD40 and carboxy-terminally of the extracellular domain of CD95L. On cells lacking CD40L, this fusion protein is poorly active with respect to CD95 activation [median effective dose (ED50)\\textgreater1 microg/ml], but it stimulates CD95 signaling with high efficiency upon binding to membrane-expressed CD40L (ED50\\textless1 ng/ml). Thus, cell surface immobilization mediated by the CD40 part of the molecule unmasks the high-latent, CD95-stimulating capacity of the otherwise poorly active CD95L fusion protein. Moreover, interaction of the CD40 part of CD40ed-CD95Led with CD40L prevents the activation of cellular CD40. The CD40ed-CD95Led fusion protein therefore simultaneously blocks antiapoptotic CD40 activation and induces CD95-mediated apoptosis. Indeed, T47D cells displaying an antiapoptotic autocrine CD40-CD40L signaling loop were significantly more sensitive toward CD40ed-CD95Led than toward soluble CD95L artificially activated by crosslinking. Fusion proteins of RANK and CD95L (RANKed-CD95Led) and CD40 and tumor necrosis factor-related apoptosis inducing ligand (TRAIL) (CD40ed-TRAILed), with domain architectures similar to CD40ed-Cd95Led, displayed RANKL-dependent CD95 and CD40L-dependent TRAILR2 activation, respectively, indicating the principle feasibility of this fusion protein design.","annote":"","author":[{"family":"Assohou-Luty","given":"Constance"},{"family":"Gerspach","given":"Jeanette"},{"family":"Siegmund","given":"Daniela"},{"family":"Müller","given":"Nicole"},{"family":"Huard","given":"Bertrand"},{"family":"Tiegs","given":"Gisa"},{"family":"Pfizenmaier","given":"Klaus"},{"family":"Wajant","given":"Harald"}],"citation-label":"Assohou-Luty2006","collection-editor":[],"collection-title":"","container-author":[],"container-title":"Journal of Molecular Medicine","documents":[],"edition":"2006/08/23","editor":[],"event-date":{"date-parts":[["2006"]],"literal":"2006"},"event-place":"","id":"ea7ad1b4d52c672f36e360d387760a0efabian","interhash":"b7520997ca1a6529152830ba3bae780a","intrahash":"ea7ad1b4d52c672f36e360d387760a0e","issue":"9","issued":{"date-parts":[["2006"]],"literal":"2006"},"keyword":"2006 izi pfizenmaier","misc":{"isbn":"0946-2716 (Print)$\\backslash$r0946-2716 (Linking)","pmid":"16924474","issn":"09462716","doi":"10.1007/s00109-006-0073-1"},"note":"","number":"9","number-of-pages":"12","page":"785--797","page-first":"785","publisher":"","publisher-place":"","status":"","title":"A CD40-CD95L fusion protein interferes with CD40L-induced prosurvival signaling and allows membrane CD40L-restricted activation of CD95","type":"article-journal","username":"fabian","version":"","volume":"84"}}