{ "types" : { "Bookmark" : { "pluralLabel" : "Bookmarks" }, "Publication" : { "pluralLabel" : "Publications" }, "GoldStandardPublication" : { "pluralLabel" : "GoldStandardPublications" }, "GoldStandardBookmark" : { "pluralLabel" : "GoldStandardBookmarks" }, "Tag" : { "pluralLabel" : "Tags" }, "User" : { "pluralLabel" : "Users" }, "Group" : { "pluralLabel" : "Groups" }, "Sphere" : { "pluralLabel" : "Spheres" } }, "properties" : { "count" : { "valueType" : "number" }, "date" : { "valueType" : "date" }, "changeDate" : { "valueType" : "date" }, "url" : { "valueType" : "url" }, "id" : { "valueType" : "url" }, "tags" : { "valueType" : "item" }, "user" : { "valueType" : "item" } }, "items" : [ { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/219d9b7ec5f5fddc9954f51b680b1a67f/pumaizi", "tags" : [ "2007","izi","morrison" ], "intraHash" : "19d9b7ec5f5fddc9954f51b680b1a67f", "interHash" : "2a6f9dd4eb8d811e82f0cc6a293bcba8", "label" : "Extending the explanatory power of live cell imaging by computationally modelling the execution of apoptotic cell death", "user" : "pumaizi", "description" : "", "date" : "2026-04-01 11:02:44", "changeDate" : "2026-04-01 11:02:44", "count" : 1, "pub-type": "inbook", "series": "Microscopy Book Series","publisher":"Formatex", "year": "2007", "url": "", "author": [ "Heinrich Huber","G Estrada","Heiko Dussmann","C connor","Markus Rehm" ], "authors": [ {"first" : "Heinrich", "last" : "Huber"}, {"first" : "G", "last" : "Estrada"}, {"first" : "Heiko", "last" : "Dussmann"}, {"first" : "C", "last" : "connor"}, {"first" : "Markus", "last" : "Rehm"} ], "editor": [ "A Méndez-Vilas","A Diaz" ], "editors": [ {"first" : "A", "last" : "Méndez-Vilas"}, {"first" : "A", "last" : "Diaz"} ], "volume": "1", "isbn" : "978-84-611-9419-3", "bibtexKey": "Huber2007" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/27062e881adf6e483d00576ed85f2598a/pumaizi", "tags" : [ "olayioye","2007","izi" ], "intraHash" : "7062e881adf6e483d00576ed85f2598a", "interHash" : "0a125a01e071b170e8b3152814482c50", "label" : "Phosphorylation of StarD10 on serine 284 by casein kinase II modulates its lipid transfer activity", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Journal of Biological Chemistry", "year": "2007", "url": "https://www.ncbi.nlm.nih.gov/pubmed/17561512", "author": [ "Monilola A. Olayioye","Michael Buchholz","Simone Schmid","Patrik Schöffler","Peter Hoffmann","Thomas Pomorski" ], "authors": [ {"first" : "Monilola A.", "last" : "Olayioye"}, {"first" : "Michael", "last" : "Buchholz"}, {"first" : "Simone", "last" : "Schmid"}, {"first" : "Patrik", "last" : "Schöffler"}, {"first" : "Peter", "last" : "Hoffmann"}, {"first" : "Thomas", "last" : "Pomorski"} ], "volume": "282","number": "31","pages": "22492--22498","abstract": "StarD10 is a dual specificity lipid transfer protein capable of shuttling phosphatidylcholine and phosphatidylethanolamine between membranes in vitro. We now provide evidence that, in vivo, StarD10 is phosphorylated on serine 284. This novel phosphorylation site was identified by tandem mass spectrometry of immunoaffinity-purified StarD10 from lysates of HEK293T cells transiently expressing the protein. In vitro kinase assays revealed that casein kinase II was capable of phosphorylating wild-type StarD10 but not a S284A mutant protein. Interestingly, hypotonic extracts prepared from HEK293T cells expressing the serine to alanine mutant exhibited increased lipid transfer activity compared with those from wild-type StarD10-expressing cells, suggesting that, in a cellular context, phosphorylation on serine 284 negatively regulates StarD10 activity. Because casein kinase II phosphorylation also inhibited lipid transfer activity of the purified recombinant StarD10 protein, inhibition is not dependent on any cellular cofactors. Instead, our data show that C-terminal StarD10 phosphorylation on serine 284 regulates its association with cellular membranes.", "isbn" : "4971168569301", "pmid" : "17561512", "issn" : "00219258", "doi" : "10.1074/jbc.M701990200", "bibtexKey": "Olayioye2007" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2a5c5141bc2e423c07e143e9012d24753/pumaizi", "tags" : [ "2007","izi","kontermann" ], "intraHash" : "a5c5141bc2e423c07e143e9012d24753", "interHash" : "671e117b60d515ec6990a1195f1a81e9", "label" : "A novel tri-functional antibody fusion protein with improved pharmacokinetic properties generated by fusing a bispecific single-chain diabody with an albumin-binding domain from streptococcal protein G", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Protein Engineering, Design and Selection", "year": "2007", "url": "https://www.ncbi.nlm.nih.gov/pubmed/17982179", "author": [ "Roland Stork","Dafne Müller","Roland E. Kontermann" ], "authors": [ {"first" : "Roland", "last" : "Stork"}, {"first" : "Dafne", "last" : "Müller"}, {"first" : "Roland E.", "last" : "Kontermann"} ], "volume": "20","number": "11","pages": "569--576","abstract": "The therapeutic application of small recombinant antibody molecules is often limited by a short serum half-life. In order to improve the pharmacokinetic properties, we have investigated a strategy utilizing fusion with an albumin-binding domain (ABD) from streptococcal protein G. This strategy was applied to a bispecific single-chain diabody (scDb CEACD3) developed for the retargeting of cytotoxic T cells to CEA-expressing tumor cells. This novel tri-functional fusion protein (scDb-ABD) was expressed in mammalian cells and recognized both antigens as well as human and mouse serum albumin. scDb-ABD was capable to retarget T cells to CEA-expressing target cells in vitro and to activate the effector cells as measured by stimulation of IL-2 release. Although activity was reduced 3-fold compared with scDb and further reduced 4-fold in the presences of human serum albumin, this assay demonstrated that scDb-ABD is active when exposed to all three antigens. Compared with scDb, the circulation time of scDb-ABD in mice was prolonged 5- to 6-fold similar to a previously described scDb-HSA fusion protein. This strategy, which adds only a small protein domain (46 amino acids) and which utilizes high-affinity, non-covalent albumin interaction, should be broadly applicable to improve serum half-lives of small recombinant antibody molecules.", "isbn" : "1741-0126 (Print)$\\backslash$r1741-0126 (Linking)", "pmid" : "17982179", "issn" : "17410126", "doi" : "10.1093/protein/gzm061", "bibtexKey": "Stork2007" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2aaea3bf6a426a593b5b98f4fc7564ae4/pumaizi", "tags" : [ "2007","izi","kulms" ], "intraHash" : "aaea3bf6a426a593b5b98f4fc7564ae4", "interHash" : "ac76f7a79f9bd9668a249c64b4885a7f", "label" : "Combined targeting of MAPK and AKT signalling pathways is a promising strategy for melanoma treatment", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "British Journal of Dermatology", "year": "2007", "url": "https://www.ncbi.nlm.nih.gov/pubmed/17388918", "author": [ "F. Meier","S. Busch","K. Lasithiotakis","D. Kulms","C. Garbe","E. Maczey","M. Herlyn","B. Schittek" ], "authors": [ {"first" : "F.", "last" : "Meier"}, {"first" : "S.", "last" : "Busch"}, {"first" : "K.", "last" : "Lasithiotakis"}, {"first" : "D.", "last" : "Kulms"}, {"first" : "C.", "last" : "Garbe"}, {"first" : "E.", "last" : "Maczey"}, {"first" : "M.", "last" : "Herlyn"}, {"first" : "B.", "last" : "Schittek"} ], "volume": "156","number": "6","pages": "1204--1213","abstract": "Background\u2002 In melanoma, several signalling pathways are constitutively activated. Among them, the RAS/RAF/MEK/ERK (MAPK) and PI3K/AKT (AKT) signalling pathways are activated through multiple mechanisms and appear to play a major role in melanoma development and progression. Objectives\u2002 In this study, we examined whether targeting the MAPK and/or AKT signalling pathways would have therapeutic effects against melanoma. Methods\u2002 Using a panel of pharmacological inhibitors (BAY 43-9006, PD98059, U0126, wortmannin, LY294002) we inhibited the MAPK and AKT signalling pathways at different levels and evaluated the effects on growth, survival and invasion of melanoma cells in monolayer and organotypic skin culture. Results\u2002 Antiproliferative and proapoptotic effects of inhibitors alone in monolayer culture were disappointing and varied among the different cell lines. In contrast, combined targeting of the MAPK and AKT signalling pathways significantly inhibited growth and enhanced apoptosis in monolayer culture. To verify our data in a more physiological context we incorporated melanoma cells into regenerated human skin mimicking the microenvironment of human melanoma. Combinations of MAPK and AKT inhibitors completely suppressed invasive tumour growth of melanoma cells in regenerated human skin. Conclusions\u2002 Combined targeting of MAPK and AKT signalling pathways is a promising strategy for melanoma treatment and should encourage further in-depth investigations.", "isbn" : "0007-0963 (Print)\n0007-0963 (Linking)", "pmid" : "17388918", "issn" : "00070963", "doi" : "10.1111/j.1365-2133.2007.07821.x", "bibtexKey": "Meier2007" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2081f6dc3e29e076983ea0100cd0d1335/pumaizi", "tags" : [ "2007","boettinger","izi" ], "intraHash" : "081f6dc3e29e076983ea0100cd0d1335", "interHash" : "6832b5bb0df2d3252b481791acf04eed", "label" : "Fast determination of conditions for maximum dynamic capacity in cation-exchange chromatography of human monoclonal antibodies", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Journal of Chromatography A", "year": "2007", "url": "https://www.ncbi.nlm.nih.gov/pubmed/17442329", "author": [ "Alexander Faude","Dörthe Zacher","Egbert Müller","Heiner Böttinger" ], "authors": [ {"first" : "Alexander", "last" : "Faude"}, {"first" : "Dörthe", "last" : "Zacher"}, {"first" : "Egbert", "last" : "Müller"}, {"first" : "Heiner", "last" : "Böttinger"} ], "volume": "1161","number": "1-2","pages": "29--35","abstract": "Dynamic binding capacity (DBC) measurements of cation-exchange resins were performed with two human monoclonal antibodies. DBC showed a pH dependent maximum, which was shifted to lower pH values with increasing buffer concentrations and increasing salting-out effect of the buffer anion according to the Hofmeister series. As this downshift correlates well with zeta potential values, a measurement of the latter allows the determination of the pH value for maximum DBC under a given set of conditions. Thus, the use of zeta potential values can accelerate the purification process development and helps to understand the protein adsorption mechanism. © 2007 Elsevier B.V. All rights reserved.", "isbn" : "0021-9673 (Print)$\\backslash$r0021-9673 (Linking)", "pmid" : "17442329", "issn" : "00219673", "doi" : "10.1016/j.chroma.2007.03.114", "bibtexKey": "Faude2007" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2a4b49d1ad08182114d0b292c26440b58/pumaizi", "tags" : [ "2007","izi","hausser" ], "intraHash" : "a4b49d1ad08182114d0b292c26440b58", "interHash" : "92ec015ebad20e21dff7d6b7e3a5be55", "label" : "Protein Kinase D regulates several aspects of development in Drosophila melanogaster", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "BMC Developmental Biology", "year": "2007", "url": "https://www.ncbi.nlm.nih.gov/pubmed/17592635", "author": [ "Dieter Maier","Anja C. Nagel","Helena Gloc","Angelika Hausser","Sabrina J. Kugler","Irmgard Wech","Anette Preiss" ], "authors": [ {"first" : "Dieter", "last" : "Maier"}, {"first" : "Anja C.", "last" : "Nagel"}, {"first" : "Helena", "last" : "Gloc"}, {"first" : "Angelika", "last" : "Hausser"}, {"first" : "Sabrina J.", "last" : "Kugler"}, {"first" : "Irmgard", "last" : "Wech"}, {"first" : "Anette", "last" : "Preiss"} ], "volume": "7","pages": "74","abstract": "BACKGROUND: Protein Kinase D (PKD) is an effector of diacylglycerol-regulated signaling pathways. Three isoforms are known in mammals that have been linked to diverse cellular functions including regulation of cell proliferation, differentiation, motility and secretory transport from the trans-Golgi network to the plasma membrane. In Drosophila, there is a single PKD orthologue, whose broad expression implicates a more general role in development. RESULTS: We have employed tissue specific overexpression of various PKD variants as well as tissue specific RNAi, in order to investigate the function of the PKD gene in Drosophila. Apart from a wild type (WT), a kinase dead (kd) and constitutively active (SE) Drosophila PKD variant, we also analyzed two human isoforms hPKD2 and hPKD3 for their capacity to substitute PKD activity in the fly. Overexpression of either WT or kd-PKD variants affected primarily wing vein development. However, overexpression of SE-PKD and PKD RNAi was deleterious. We observed tissue loss, wing defects and degeneration of the retina. The latter phenotype conforms to a role of PKD in the regulation of cytoskeletal dynamics. Strongest phenotypes were larval to pupal lethality. RNAi induced phenotypes could be rescued by a concurrent overexpression of Drosophila wild type PKD or either human isoform hPKD2 and hPKD3. CONCLUSION: Our data confirm the hypothesis that Drosophila PKD is a multifunctional kinase involved in diverse processes such as regulation of the cytoskeleton, cell proliferation and death as well as differentiation of various fly tissues.", "isbn" : "1471-213X (Electronic)\n1471-213X (Linking)", "pmid" : "17592635", "issn" : "1471213X", "doi" : "10.1186/1471-213X-7-74", "bibtexKey": "Maier2007" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2b06b802c63be71124826bfc3f564a366/pumaizi", "tags" : [ "sauter","2007","izi","kulms" ], "intraHash" : "b06b802c63be71124826bfc3f564a366", "interHash" : "807cf281961bb7ca58c7db4c390a3291", "label" : "Modeling of IL-1 induced NF-κB signaling and analysis of additional UVB influence", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "inproceedings", "booktitle": "Proceedings of the SICE Annual Conference", "year": "2007", "url": "https://doi.org/10.1109/SICE.2007.4421193", "author": [ "Johannes Witt","Sebastian Husser","Dagmar Kulms","Sandra Barisic","Oliver Sawodny","Thomas Sauter" ], "authors": [ {"first" : "Johannes", "last" : "Witt"}, {"first" : "Sebastian", "last" : "Husser"}, {"first" : "Dagmar", "last" : "Kulms"}, {"first" : "Sandra", "last" : "Barisic"}, {"first" : "Oliver", "last" : "Sawodny"}, {"first" : "Thomas", "last" : "Sauter"} ], "pages": "1353--1358","abstract": "NF-$\\kappa$B dependent enhancement of UVB-induced apoptosis has recently been reported upon co-stimulation of cells with IL-1, together with a sustained absence of the NF-$\\kappa$B inhibitor IKBOC. In order to investigate the behavior of I$\\kappa$B$\\alpha$, an ODE model for the IL-1 receptor is developed, coupled with an existing NF-$\\kappa$B signaling module and parameterized using experimental and literature data. Functional dependencies between good fit parameters facilitate parameter identification for additional experimental data. The model is used to test and reject the hypothesis that the sustained absence of I$\\kappa$B$\\alpha$ upon IL-1+UVB stimulation is due to an altered internalization behavior of the IL-1 receptor. © 2007 SICE.", "isbn" : "4907764286", "doi" : "10.1109/SICE.2007.4421193", "bibtexKey": "Witt2007" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/237256a523f717f6183001982b4f673b7/pumaizi", "tags" : [ "2007","izi","pfizenmaier","hausser" ], "intraHash" : "37256a523f717f6183001982b4f673b7", "interHash" : "7af73a02ead39b71c60d30c3ee3f2194", "label" : "Angiotensin II stimulates protein kinase D-dependent histone deacetylase 5 phosphorylation and nuclear export leading to vascular smooth muscle cell hypertrophy", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Arteriosclerosis, Thrombosis, and Vascular Biology", "year": "2007", "url": "https://www.ncbi.nlm.nih.gov/pubmed/17823368", "author": [ "Xiangbin Xu","Chang Hoon Ha","Chelsea Wong","Weiye Wang","Angelika Hausser","Klaus Pfizenmaier","Eric N. Olson","Timothy A. McKinsey","Zheng Gen Jin" ], "authors": [ {"first" : "Xiangbin", "last" : "Xu"}, {"first" : "Chang Hoon", "last" : "Ha"}, {"first" : "Chelsea", "last" : "Wong"}, {"first" : "Weiye", "last" : "Wang"}, {"first" : "Angelika", "last" : "Hausser"}, {"first" : "Klaus", "last" : "Pfizenmaier"}, {"first" : "Eric N.", "last" : "Olson"}, {"first" : "Timothy A.", "last" : "McKinsey"}, {"first" : "Zheng Gen", "last" : "Jin"} ], "volume": "27","number": "11","pages": "2355--2362","abstract": "BACKGROUND: Angiotensin II (Ang II) induces the phenotypic modulation and hypertrophy of vascular smooth muscle cells (VSMCs), which is implicated in the pathogenesis of hypertension, atherosclerosis, and diabetes. In this study, we tested the hypothesis that histone deacetylases 5 (HDAC5) and its signal pathway play a role in Ang II-induced VSMC hypertrophy. METHODS AND RESULTS: VSMCs were isolated from the thoracic aortas of male Sprague-Dawley rats and treated with Ang II. We found that Ang II rapidly stimulated phosphorylation of HDAC5 at Serine259/498 residues in a time- and dose- dependent manner. Ang II receptor-1, protein kinase C, and protein kinase D1 (PKD1) mediated HDAC5 phosphorylation. Furthermore, we observed that Ang II stimulated HDAC5 nuclear export, which was dependent on its PKD1-dependent phosphorylation. Consequently, both inhibiting PKD1 and HDAC5 Serine259/498 to Alanine mutant significantly attenuated Ang II-induced myocyte enhancer factor-2 (MEF2) transcriptional activity and protein synthesis in VSMCs. CONCLUSION: These findings demonstrate for the first time that PKD1-dependent HDAC5 phosphorylation and nuclear export mediates Ang II-induced MEF2 activation and VSMC hypertrophy, and suggest that PKD1 and HDAC5 may emerge as potential targets for the treatment of pathological vascular hypertrophy.", "isbn" : "1524-4636 (Electronic)$\\backslash$r1079-5642 (Linking)", "pmid" : "17823368", "eprint" : "NIHMS150003", "issn" : "10795642", "archiveprefix" : "arXiv", "arxivid" : "NIHMS150003", "doi" : "10.1161/ATVBAHA.107.151704", "bibtexKey": "Xu2007" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2af758bfac00a59ff43eaa827cc5741da/pumaizi", "tags" : [ "2007","izi","kontermann" ], "intraHash" : "af758bfac00a59ff43eaa827cc5741da", "interHash" : "2f6d8bf481e5fba7e7d1d62700ab2211", "label" : "Single-chain Fv immunoliposomes for the targeting of fibroblast activation protein-expressing tumor stromal cells", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Journal of Drug Targeting", "year": "2007", "url": "https://www.ncbi.nlm.nih.gov/pubmed/17613658", "author": [ "Patrick Baum","Dafne Müller","Ronny Rüger","Roland E. Kontermann" ], "authors": [ {"first" : "Patrick", "last" : "Baum"}, {"first" : "Dafne", "last" : "Müller"}, {"first" : "Ronny", "last" : "Rüger"}, {"first" : "Roland E.", "last" : "Kontermann"} ], "volume": "15","number": "6","pages": "399--406","abstract": "Tumor stromal cells have gained increasing attention as possible target for cancer therapy. Fibroblast activation protein (FAP) represents a cell surface antigen selectively expressed by reactive tumor stromal fibroblasts of various cancers. Here, we describe anti-FAP immunoliposomes as carrier systems for active targeting of FAP-expressing cells. As targeting ligand we used single-chain Fv (scFv) molecules cross-reacting with human and mouse FAP. These scFv molecules were genetically modified to express an additional cysteine residue at the C-terminus allowing a defined and site-directed conjugation. Coupling to Mal-PEG(2000)-DSPE containing liposomes resulted in sterically stabilized scFv immunoliposomes showing strong and specific binding to FAP-expressing cells. These immunoliposomes were highly stable when incubated under physiological conditions (human plasma, 37 degrees C). In addition, we could show that binding to FAP-expressing cells leads to internalization of intact liposomes into the endosomal compartment. Thus, these anti-FAP scFv immunoliposomes should be suitable for target cell-specific delivery and uptake of encapsulated drugs.", "isbn" : "1061-186X (Print)\n1026-7158 (Linking)", "pmid" : "17613658", "issn" : "1061186X", "doi" : "10.1080/10611860701453034", "bibtexKey": "Baum2007" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2acc636b43791edf13219f9a0c6cf4993/pumaizi", "tags" : [ "2007","izi","kontermann" ], "intraHash" : "acc636b43791edf13219f9a0c6cf4993", "interHash" : "e004ac2e0d4b7129aa787619d0b514b0", "label" : "Tropism Modification of Adenovirus Vectors by Peptide Ligand Insertion into Various Positions of the Adenovirus Serotype 41 Short-Fiber Knob Domain", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Journal of Virology", "year": "2007", "url": "http://jvi.asm.org/cgi/doi/10.1128/JVI.02722-06", "author": [ "A. Hesse","D. Kosmides","R. E. Kontermann","D. M. Nettelbeck" ], "authors": [ {"first" : "A.", "last" : "Hesse"}, {"first" : "D.", "last" : "Kosmides"}, {"first" : "R. E.", "last" : "Kontermann"}, {"first" : "D. M.", "last" : "Nettelbeck"} ], "volume": "81","number": "6","pages": "2688--2699","abstract": "Recombinant adenoviruses have emerged as promising agents in therapeutic gene transfer, genetic vaccination, and viral oncolysis. Therapeutic applications of adenoviruses, however, would benefit substantially from targeted virus cell entry, for example, into cancer or immune cells, as opposed to the broad tropism that adenoviruses naturally possess. Such tropism modification of adenoviruses requires the deletion of their natural cell binding properties and the incorporation of cell binding ligands. The short fibers of subgroup F adenoviruses have recently been suggested as a tool for genetic adenovirus detargeting based on the reduced infectivity of corresponding adenovectors with chimeric fibers in vitro and in vivo. The goal of our study was to determine functional insertion sites for peptide ligands in the adenovirus serotype 41 (Ad41) short fiber knob. With a model peptide, CDCRGDCFC, we could demonstrate that ligand incorporation into three of five analyzed loops of the knob, namely, EG, HI, and IJ, is feasible without a loss of fiber trimerization. The resulting adenovectors showed enhanced infectivity for various cell types, which was superior to that of viruses with the same peptide fused to the fiber C terminus. Strategies to further augment gene transfer efficacy by extension of the fiber shaft, insertion of tandem copies of the ligand peptide, or extension of the ligand-flanking linkers failed, indicating that precise ligand positioning is pivotal. Our study establishes that internal ligand incorporation into a short-shafted adenovirus fiber is feasible and suggests the Ad41 short fiber with ligand insertion into the top (IJ loop) or side (EG and HI loops) of the knob domain as a novel platform for genetic targeting of therapeutic adenoviruses.", "isbn" : "0022-538X (Print)$\\backslash$r0022-538X (Linking)", "pmid" : "17192304", "issn" : "0022-538X", "doi" : "10.1128/JVI.02722-06", "bibtexKey": "Hesse2007" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/27d2b8f98400afae3b13cdb620137d949/pumaizi", "tags" : [ "2007","izi","pfizenmaier" ], "intraHash" : "7d2b8f98400afae3b13cdb620137d949", "interHash" : "480a08206d600534b7779157eea446bb", "label" : "Enforced covalent trimerization increases the activity of the TNF ligand family members TRAIL and CD95L", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Cell Death and Differentiation", "year": "2007", "url": "https://www.ncbi.nlm.nih.gov/pubmed/17703232", "author": [ "D. Berg","M. Lehne","N. Müller","D. Siegmund","S. Münkel","W. Sebald","K. Pfizenmaier","H. Wajant" ], "authors": [ {"first" : "D.", "last" : "Berg"}, {"first" : "M.", "last" : "Lehne"}, {"first" : "N.", "last" : "Müller"}, {"first" : "D.", "last" : "Siegmund"}, {"first" : "S.", "last" : "Münkel"}, {"first" : "W.", "last" : "Sebald"}, {"first" : "K.", "last" : "Pfizenmaier"}, {"first" : "H.", "last" : "Wajant"} ], "volume": "14","number": "12","pages": "2021--2034","abstract": "Variants of human TRAIL (hTRAIL) and human CD95L (hCD95L), encompassing the TNF homology domain (THD), interact with the corresponding receptors and stimulate CD95 and TRAILR2 signaling after cross-linking. The murine counterparts (mTRAIL, mCD95L) showed no or only low receptor binding and were inactive/poorly active after cross-linking. The stalk region preceding the THD of mCD95L conferred secondary aggregation and restored CD95 activation in the absence of cross-linking. A corresponding variant of mTRAIL, however, was still not able to activate TRAIL death receptors, but gained good activity after cross-linking. Notably, disulfide-bonded fusion proteins of the THD of mTRAIL and mCD95L with a subdomain of the tenascin-C (TNC) oligomerization domain, which still assembled into trimers, efficiently interacted with their cognate cellular receptors and robustly stimulated CD95 and TRAILR2 signaling after secondary cross-linking. Introduction of the TNC domain also further enhanced the activity of THD encompassing variants of hTRAIL and hCD95L. Thus, spatial fixation of the N-terminus of the THD appears necessary in some TNF ligands to ensure proper receptor binding. This points to yet unanticipated functions of the stalk and/or transmembrane region of TNF ligands for the functionality of these molecules and offers a broadly applicable option to generate recombinant soluble ligands of the TNF family with superior activity.", "isbn" : "1350-9047", "pmid" : "17703232", "issn" : "13509047", "doi" : "10.1038/sj.cdd.4402213", "bibtexKey": "Berg2007" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/24c9f5da9529f7feb43d02eee34cf053c/pumaizi", "tags" : [ "olayioye","2007","izi","pfizenmaier","hausser" ], "intraHash" : "4c9f5da9529f7feb43d02eee34cf053c", "interHash" : "679c72b8dd58f26768d8fe98fac798ca", "label" : "Regulation of secretory transport by protein kinase D-mediated phosphorylation of the ceramide transfer protein", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Journal of Cell Biology", "year": "2007", "url": "https://www.ncbi.nlm.nih.gov/pubmed/17591919", "author": [ "Tim Fugmann","Angelika Hausser","Patrik Schöffler","Simone Schmid","Klaus Pfizenmaier","Monilola A. Olayioye" ], "authors": [ {"first" : "Tim", "last" : "Fugmann"}, {"first" : "Angelika", "last" : "Hausser"}, {"first" : "Patrik", "last" : "Schöffler"}, {"first" : "Simone", "last" : "Schmid"}, {"first" : "Klaus", "last" : "Pfizenmaier"}, {"first" : "Monilola A.", "last" : "Olayioye"} ], "volume": "178","number": "1","pages": "15--22","abstract": "Protein kinase D (PKD) has been identified as a crucial regulator of secretory transport at the trans-Golgi network (TGN). Recruitment and activation of PKD at the TGN is mediated by the lipid diacylglycerol, a pool of which is generated by sphingomyelin synthase from ceramide and phosphatidylcholine. The nonvesicular transfer of ceramide from the endoplasmic reticulum to the Golgi complex is mediated by the lipid transfer protein CERT (ceramide transport). In this study, we identify CERT as a novel in vivo PKD substrate. Phosphorylation on serine 132 by PKD decreases the affinity of CERT toward its lipid target phosphatidylinositol 4-phosphate at Golgi membranes and reduces ceramide transfer activity, identifying PKD as a regulator of lipid homeostasis. We also show that CERT, in turn, is critical for PKD activation and PKD-dependent protein cargo transport to the plasma membrane. Thus, the interdependence of PKD and CERT is key to the maintenance of Golgi membrane integrity and secretory transport.", "isbn" : "0021-9525 (Print)$\\backslash$r0021-9525 (Linking)", "pmid" : "17591919", "issn" : "00219525", "doi" : "10.1083/jcb.200612017", "bibtexKey": "Fugmann2007" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2ee14d3a1862f9d0be1bf8b95e06fcde1/pumaizi", "tags" : [ "2007","izi","pfizenmaier","hausser" ], "intraHash" : "ee14d3a1862f9d0be1bf8b95e06fcde1", "interHash" : "2a14426ea713a0dcfa2b60b429ce51b1", "label" : "PKD is recruited to sites of actin remodelling at the leading edge and negatively regulates cell migration", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "FEBS Letters", "year": "2007", "url": "https://www.ncbi.nlm.nih.gov/pubmed/17707375", "author": [ "Tim Eiseler","Michael A. Schmid","Fitnat Topbas","Klaus Pfizenmaier","Angelika Hausser" ], "authors": [ {"first" : "Tim", "last" : "Eiseler"}, {"first" : "Michael A.", "last" : "Schmid"}, {"first" : "Fitnat", "last" : "Topbas"}, {"first" : "Klaus", "last" : "Pfizenmaier"}, {"first" : "Angelika", "last" : "Hausser"} ], "volume": "581","number": "22","pages": "4279--4287","abstract": "Protein kinase D (PKD) has been implicated in the regulation of cell shape, adhesion, and migration. At the leading edge of migrating cells active PKD co-localizes with F-actin, Arp3 and cortactin. Platelet derived growth factor (PDGF) activates PKD and recruits the kinase to the leading edge, suggesting a role for PKD in actin remodelling. In support of this, PKD directly interacts with F-actin and phosphorylates cortactin in vitro. Interference with PKD function by overexpression of a dominant negative PKD or by PKD-specific siRNA enhanced cell migration, whereas cells overexpressing PKD wild type displayed reduced migratory potential. Taken together, these data reveal a negative regulatory function of PKD in cell migration. © 2007 Federation of European Biochemical Societies.", "isbn" : "0014-5793 (Print)$\\backslash$r0014-5793 (Linking)", "pmid" : "17707375", "issn" : "00145793", "doi" : "10.1016/j.febslet.2007.07.079", "bibtexKey": "Eiseler2007" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/23793e7366c6eb28b539412cd0cf89239/pumaizi", "tags" : [ "2007","izi","mueller","kontermann" ], "intraHash" : "3793e7366c6eb28b539412cd0cf89239", "interHash" : "e897c4ac1c23d8623b963761ae81b802", "label" : "Improved pharmacokinetics of recombinant bispecific antibody molecules by fusion to human serum albumin", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Journal of Biological Chemistry", "year": "2007", "url": "https://www.ncbi.nlm.nih.gov/pubmed/17347147", "author": [ "Dafne Müller","Anette Karle","Bettina Meißburger","Ines Höfig","Roland Stork","Roland E. Kontermann" ], "authors": [ {"first" : "Dafne", "last" : "Müller"}, {"first" : "Anette", "last" : "Karle"}, {"first" : "Bettina", "last" : "Meißburger"}, {"first" : "Ines", "last" : "Höfig"}, {"first" : "Roland", "last" : "Stork"}, {"first" : "Roland E.", "last" : "Kontermann"} ], "volume": "282","number": "17","pages": "12650--12660","abstract": "Recombinant bispecific antibodies such as tandem scFv molecules (taFv), diabodies (Db), or single chain diabodies (scDb) have shown to be able to retarget T lymphocytes to tumor cells, leading to their destruction. However, therapeutic efficacy is hampered by a short serum half-life of these small molecules having molecule masses of 50-60 kDa. Thus, improvement of the pharmacokinetic properties of small bispecific antibody formats is required to enhance efficacy in vivo. In this study, we generated several recombinant bispecific antibody-albumin fusion proteins and analyzed these molecules for biological activity and pharmacokinetic properties. Three recombinant antibody formats were produced by fusing two different scFv molecules, bispecific scDb or taFv molecules, respectively, to human serum albumin (HSA). These constructs (scFv(2)-HSA, scDb-HSA, taFv-HSA), directed against the tumor antigen carcinoembryonic antigen (CEA) and the T cell receptor complex molecule CD3, retained full binding capacity to both antigens compared with unfused scFv, scDb, and taFv molecules. Tumor antigen-specific retargeting and activation of T cells as monitored by interleukin-2 release was observed for scDb, scDb-HSA, taFv-HSA, and to a lesser extent for scFv(2)-HSA. T cell activation could be further enhanced by a target cell-specific costimulatory signal provided by a B7-DbCEA fusion protein. Furthermore, we could demonstrate that fusion to serum albumin strongly increases circulation time of recombinant bispecific antibodies. In addition, our comparative study indicates that single chain diabody-albumin fusion proteins seem to be the most promising format for further studying cytotoxic activities in vitro and in vivo.", "isbn" : "1265012660", "pmid" : "17347147", "issn" : "00219258", "doi" : "10.1074/jbc.M700820200", "bibtexKey": "Muller2007" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/250cf936f2051540a79a54a41e0098130/pumaizi", "tags" : [ "2007","izi","mueller","kontermann" ], "intraHash" : "50cf936f2051540a79a54a41e0098130", "interHash" : "c006c3d20cedb23ace3508f0b936a84f", "label" : "Recombinant bispecific antibodies for cellular cancer immunotherapy", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Current opinion in molecular therapeutics", "year": "2007", "url": "https://www.ncbi.nlm.nih.gov/pubmed/17694444", "author": [ "Dafne Müller","Roland E Kontermann" ], "authors": [ {"first" : "Dafne", "last" : "Müller"}, {"first" : "Roland E", "last" : "Kontermann"} ], "volume": "9","number": "4","pages": "319","abstract": "Bispecific antibodies recognizing two different antigens present on different cells have been developed for cellular cancer therapy in which cytotoxic effector cells are recruited to tumor cells. Initial studies with bispecific antibodies have not reached satisfactory clinical endpoints, mainly due to low efficacy, Fc-mediated side effects and immunogenicity. This has resulted in a declining interest in bispecific antibodies for cancer therapy. However, growing knowledge in effector cell biology and the implementation of antibody engineering technologies has led to a revival and the development of novel or improved strategies. Various recombinant bispecific antibodies have demonstrated efficacy in vitro andin vivo, with the first recombinant antibody molecule currently in clinical trials for the treatment of B-cell malignancies.", "isbn" : "1464-8431", "pmid" : "17694444", "issn" : "1464-8431", "bibtexKey": "Muller2007a" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2126bc50798c9d003b5140d4eb20517fa/pumaizi", "tags" : [ "2007","izi","scheuric" ], "intraHash" : "126bc50798c9d003b5140d4eb20517fa", "interHash" : "39fe8aaa8af8ee72c23ffc349d4f6b31", "label" : "Steady state and (bi-) stability evaluation of simple protease signalling networks", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 7, "pub-type": "article", "journal": "Biosystems", "year": "2007", "url": "http://www.ncbi.nlm.nih.gov/pubmed/17314003", "author": [ "Thomas Eißing","Steffen Waldherr","Frank Allgöwer","Peter Scheurich","Eric Bullinger" ], "authors": [ {"first" : "Thomas", "last" : "Eißing"}, {"first" : "Steffen", "last" : "Waldherr"}, {"first" : "Frank", "last" : "Allgöwer"}, {"first" : "Peter", "last" : "Scheurich"}, {"first" : "Eric", "last" : "Bullinger"} ], "volume": "90","number": "3","pages": "591--601","abstract": "Signal transduction networks are complex, as are their mathematical models. Gaining a deeper understanding requires a system analysis. Important aspects are the number, location and stability of steady states. In particular, bistability has been recognised as an important feature to achieve molecular switching. This paper compares different model structures and analysis methods particularly useful for bistability analysis. The biological applications include proteolytic cascades as, for example, encountered in the apoptotic signalling pathway or in the blood clotting system. We compare three model structures containing zero-order, inhibitor and cooperative ultrasensitive reactions, all known to achieve bistability. The combination of phase plane and bifurcation analysis provides an illustrative and comprehensive understanding of how bistability can be achieved and indicates how robust this behaviour is. Experimentally, some so-called \"inactive\" components were shown to have a residual activity. This has been mostly ignored in mathematical models. Our analysis reveals that bistability is only mildly affected in the case of zero-order or inhibitor ultrasensitivity. However, the case where bistability is achieved by cooperative ultrasensitivity is severely affected by this perturbation.", "pmid" : "17314003", "issn" : "03032647", "doi" : "10.1016/j.biosystems.2007.01.003", "bibtexKey": "Eißing2007" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2cde947ddd81d2bb403f18f6e1b3713db/pumaizi", "tags" : [ "2007","izi","scheuric" ], "intraHash" : "cde947ddd81d2bb403f18f6e1b3713db", "interHash" : "219c97ac79b839039ffffec924a82121", "label" : "Response to bistability in apoptosis: Roles of Bax, Bcl-2, and mitochondrial permeability transition pores", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 7, "pub-type": "article", "journal": "Biophysical Journal", "year": "2007", "url": "https://www.ncbi.nlm.nih.gov/pubmed/17277182", "author": [ "Thomas Eissing","Steffen Waldherr","Frank Allgöwer","Peter Scheurich","Eric Bullinger" ], "authors": [ {"first" : "Thomas", "last" : "Eissing"}, {"first" : "Steffen", "last" : "Waldherr"}, {"first" : "Frank", "last" : "Allgöwer"}, {"first" : "Peter", "last" : "Scheurich"}, {"first" : "Eric", "last" : "Bullinger"} ], "volume": "92","number": "9","pages": "3332--3334","abstract": "Recently, a mathematical model of the mitochondrial apoptotic pathway was proposed. In that study, the robustness of different simplified signaling models with respect to parameter changes was also investigated. It was found that bistability achieved via cooperative ultrasensitivity is \"much more robust\" than other mechanisms such as inhibitor ultrasensitivity. We reinvestigate this interesting finding to reveal that it does not hold in such generality. Our results indicate that mechanisms other than cooperative ultrasensitivity, such as inhibitor ultrasensitivity, can confer a similar robust bistable performance. Thereby, these findings are not restricted to apoptosis signaling, but relevant to bistable signaling in general. In addition, example calculations indicate the potential practical relevance of inhibitor ultrasensitivity for generating robustness in apoptosis signaling. © 2007 by the Biophysical Society.", "isbn" : "4971168567", "pmid" : "16339882", "issn" : "00063495", "doi" : "10.1529/biophysj.106.100362", "bibtexKey": "Eissing2007" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/23793e7366c6eb28b539412cd0cf89239/fabian", "tags" : [ "2007","izi","mueller","kontermann" ], "intraHash" : "3793e7366c6eb28b539412cd0cf89239", "interHash" : "e897c4ac1c23d8623b963761ae81b802", "label" : "Improved pharmacokinetics of recombinant bispecific antibody molecules by fusion to human serum albumin", "user" : "fabian", "description" : "", "date" : "2023-06-29 13:07:55", "changeDate" : "2023-06-29 13:07:55", "count" : 3, "pub-type": "article", "journal": "Journal of Biological Chemistry", "year": "2007", "url": "https://www.ncbi.nlm.nih.gov/pubmed/17347147", "author": [ "Dafne Müller","Anette Karle","Bettina Meißburger","Ines Höfig","Roland Stork","Roland E. Kontermann" ], "authors": [ {"first" : "Dafne", "last" : "Müller"}, {"first" : "Anette", "last" : "Karle"}, {"first" : "Bettina", "last" : "Meißburger"}, {"first" : "Ines", "last" : "Höfig"}, {"first" : "Roland", "last" : "Stork"}, {"first" : "Roland E.", "last" : "Kontermann"} ], "volume": "282","number": "17","pages": "12650--12660","abstract": "Recombinant bispecific antibodies such as tandem scFv molecules (taFv), diabodies (Db), or single chain diabodies (scDb) have shown to be able to retarget T lymphocytes to tumor cells, leading to their destruction. However, therapeutic efficacy is hampered by a short serum half-life of these small molecules having molecule masses of 50-60 kDa. Thus, improvement of the pharmacokinetic properties of small bispecific antibody formats is required to enhance efficacy in vivo. In this study, we generated several recombinant bispecific antibody-albumin fusion proteins and analyzed these molecules for biological activity and pharmacokinetic properties. Three recombinant antibody formats were produced by fusing two different scFv molecules, bispecific scDb or taFv molecules, respectively, to human serum albumin (HSA). These constructs (scFv(2)-HSA, scDb-HSA, taFv-HSA), directed against the tumor antigen carcinoembryonic antigen (CEA) and the T cell receptor complex molecule CD3, retained full binding capacity to both antigens compared with unfused scFv, scDb, and taFv molecules. Tumor antigen-specific retargeting and activation of T cells as monitored by interleukin-2 release was observed for scDb, scDb-HSA, taFv-HSA, and to a lesser extent for scFv(2)-HSA. T cell activation could be further enhanced by a target cell-specific costimulatory signal provided by a B7-DbCEA fusion protein. Furthermore, we could demonstrate that fusion to serum albumin strongly increases circulation time of recombinant bispecific antibodies. In addition, our comparative study indicates that single chain diabody-albumin fusion proteins seem to be the most promising format for further studying cytotoxic activities in vitro and in vivo.", "isbn" : "1265012660", "pmid" : "17347147", "issn" : "00219258", "doi" : "10.1074/jbc.M700820200", "bibtexKey": "Muller2007" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2b06b802c63be71124826bfc3f564a366/fabian", "tags" : [ "sauter","2007","izi","kulms" ], "intraHash" : "b06b802c63be71124826bfc3f564a366", "interHash" : "807cf281961bb7ca58c7db4c390a3291", "label" : "Modeling of IL-1 induced NF-κB signaling and analysis of additional UVB influence", "user" : "fabian", "description" : "", "date" : "2023-06-29 13:07:55", "changeDate" : "2023-06-29 13:07:55", "count" : 3, "pub-type": "inproceedings", "booktitle": "Proceedings of the SICE Annual Conference", "year": "2007", "url": "https://doi.org/10.1109/SICE.2007.4421193", "author": [ "Johannes Witt","Sebastian Husser","Dagmar Kulms","Sandra Barisic","Oliver Sawodny","Thomas Sauter" ], "authors": [ {"first" : "Johannes", "last" : "Witt"}, {"first" : "Sebastian", "last" : "Husser"}, {"first" : "Dagmar", "last" : "Kulms"}, {"first" : "Sandra", "last" : "Barisic"}, {"first" : "Oliver", "last" : "Sawodny"}, {"first" : "Thomas", "last" : "Sauter"} ], "pages": "1353--1358","abstract": "NF-$\\kappa$B dependent enhancement of UVB-induced apoptosis has recently been reported upon co-stimulation of cells with IL-1, together with a sustained absence of the NF-$\\kappa$B inhibitor IKBOC. In order to investigate the behavior of I$\\kappa$B$\\alpha$, an ODE model for the IL-1 receptor is developed, coupled with an existing NF-$\\kappa$B signaling module and parameterized using experimental and literature data. Functional dependencies between good fit parameters facilitate parameter identification for additional experimental data. The model is used to test and reject the hypothesis that the sustained absence of I$\\kappa$B$\\alpha$ upon IL-1+UVB stimulation is due to an altered internalization behavior of the IL-1 receptor. © 2007 SICE.", "isbn" : "4907764286", "doi" : "10.1109/SICE.2007.4421193", "bibtexKey": "Witt2007" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/27d2b8f98400afae3b13cdb620137d949/fabian", "tags" : [ "2007","izi","pfizenmaier" ], "intraHash" : "7d2b8f98400afae3b13cdb620137d949", "interHash" : "480a08206d600534b7779157eea446bb", "label" : "Enforced covalent trimerization increases the activity of the TNF ligand family members TRAIL and CD95L", "user" : "fabian", "description" : "", "date" : "2023-06-29 13:07:55", "changeDate" : "2023-06-29 13:07:55", "count" : 3, "pub-type": "article", "journal": "Cell Death and Differentiation", "year": "2007", "url": "https://www.ncbi.nlm.nih.gov/pubmed/17703232", "author": [ "D. Berg","M. Lehne","N. Müller","D. Siegmund","S. Münkel","W. Sebald","K. Pfizenmaier","H. Wajant" ], "authors": [ {"first" : "D.", "last" : "Berg"}, {"first" : "M.", "last" : "Lehne"}, {"first" : "N.", "last" : "Müller"}, {"first" : "D.", "last" : "Siegmund"}, {"first" : "S.", "last" : "Münkel"}, {"first" : "W.", "last" : "Sebald"}, {"first" : "K.", "last" : "Pfizenmaier"}, {"first" : "H.", "last" : "Wajant"} ], "volume": "14","number": "12","pages": "2021--2034","abstract": "Variants of human TRAIL (hTRAIL) and human CD95L (hCD95L), encompassing the TNF homology domain (THD), interact with the corresponding receptors and stimulate CD95 and TRAILR2 signaling after cross-linking. The murine counterparts (mTRAIL, mCD95L) showed no or only low receptor binding and were inactive/poorly active after cross-linking. The stalk region preceding the THD of mCD95L conferred secondary aggregation and restored CD95 activation in the absence of cross-linking. A corresponding variant of mTRAIL, however, was still not able to activate TRAIL death receptors, but gained good activity after cross-linking. Notably, disulfide-bonded fusion proteins of the THD of mTRAIL and mCD95L with a subdomain of the tenascin-C (TNC) oligomerization domain, which still assembled into trimers, efficiently interacted with their cognate cellular receptors and robustly stimulated CD95 and TRAILR2 signaling after secondary cross-linking. Introduction of the TNC domain also further enhanced the activity of THD encompassing variants of hTRAIL and hCD95L. Thus, spatial fixation of the N-terminus of the THD appears necessary in some TNF ligands to ensure proper receptor binding. This points to yet unanticipated functions of the stalk and/or transmembrane region of TNF ligands for the functionality of these molecules and offers a broadly applicable option to generate recombinant soluble ligands of the TNF family with superior activity.", "isbn" : "1350-9047", "pmid" : "17703232", "issn" : "13509047", "doi" : "10.1038/sj.cdd.4402213", "bibtexKey": "Berg2007" } ] }