{ "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/200458f156ebde46506df6d84f166689a/pumaizi", "tags" : [ "2009","izi","morrison" ], "intraHash" : "00458f156ebde46506df6d84f166689a", "interHash" : "90db89b73d1dc3844a6763c1f824f2d9", "label" : "Systems Biology Approaches to the Study of Apoptosis", "user" : "pumaizi", "description" : "", "date" : "2026-04-01 10:51:07", "changeDate" : "2026-04-01 10:51:07", "count" : 1, "pub-type": "inbook", "booktitle": "Essentials of Apoptosis: A Guide for Basic and Clinical Research","publisher":"Humana Press","address":"Totowa, NJ", "year": "2009", "url": "https://doi.org/10.1007/978-1-60327-381-7_12", "author": [ "Heinrich Huber","Eric Bullinger","Markus Rehm" ], "authors": [ {"first" : "Heinrich", "last" : "Huber"}, {"first" : "Eric", "last" : "Bullinger"}, {"first" : "Markus", "last" : "Rehm"} ], "editor": [ "Zheng Dong","Xiao-Ming Yin" ], "editors": [ {"first" : "Zheng", "last" : "Dong"}, {"first" : "Xiao-Ming", "last" : "Yin"} ], "pages": "283--297","abstract": "Today, we can avail of comprehensive information on the molecular mechanisms of apoptosis signaling that was gathered during decades of intense research. This chapter presents how mathematical approaches in the field of cellular signaling are used to integrate this complex and heterogeneous information into computational models with the aim to elucidate the functional properties of apoptotic signaling networks. Mathematical modeling allows one to describe properties of signaling systems that emanate from the interplay of the system's individual components and has a longstanding and successful history in the fields of physics, chemistry, and their applied engineering sciences. Systems analyses can serve to describe and identify signaling dynamics, molecular switches, thresholds, and feedback regulatory mechanisms and allow systems properties such as stability and robustness toward external perturbations to be identified. Crucially, systems analyses can also serve to generate novel qualitative and quantitative research hypotheses, which in turn allow for more focused experimental research approaches. This chapter provides a concise and critical overview on the current state of systems biology in the field of apoptotic signaling and the methodology employed.", "isbn" : "978-1-60327-381-7", "doi" : "10.1007/978-1-60327-381-7_12", "bibtexKey": "Huber2009" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/233604f804d5c960f7b8297d158ea9253/pumaizi", "tags" : [ "2009","izi","kulms" ], "intraHash" : "33604f804d5c960f7b8297d158ea9253", "interHash" : "4e1b53ef4f07c7615d1effeba80dcb97", "label" : "Sensitization of melanoma cells to TRAIL by UVB-induced and NF-κB-mediated downregulation of xIAP", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Oncogene", "year": "2009", "url": "https://www.ncbi.nlm.nih.gov/pubmed/18978816", "author": [ "B. Thayaparasingham","A. Kunz","D. Kulms" ], "authors": [ {"first" : "B.", "last" : "Thayaparasingham"}, {"first" : "A.", "last" : "Kunz"}, {"first" : "D.", "last" : "Kulms"} ], "volume": "28","number": "3","pages": "345--362","abstract": "Effective treatment of malignant melanoma with the tumor-selective death ligand tumor necrosis-related apoptosis-inducing ligand (TRAIL) is curtailed by the fact that many melanoma cell lines are a priori resistant against TRAIL-induced apoptosis. By investigating 18 melanoma cell lines, we show that TRAIL susceptibility is completely independent of the tumor progression stage but can be positively stimulated by co-exposure to a sublethal ultraviolet B light (UVB) dose, providing an excellent tool to study the mechanism underlying TRAIL resistance. TRAIL resistance could be linked to the ratio of x-linked inhibitor of apoptosis proteins (xIAP) and caspase-3 levels within the cell. UVB-induced sensitization coincides with enhanced xIAP degradation, allowing full caspase-3 processing and activation. It is also accompanied by concomitant IkappaBalpha degradation, resulting in nuclear factor-kappaB (NF-kappaB)-dependent transcriptional repression of xIAP. Loss of xIAP in turn was reduced upon overexpression of an IkappaBalpha super-repressor, thus NF-kappaB activation seems to be responsible for differential regulation of xIAP and consequently determines TRAIL susceptibility. As xIAP-mediated blockade of apoptosis seems to be the dominant cause of TRAIL resistance of all melanoma cell lines investigated here, our data suggest that direct chemical xIAP inhibition or combination treatment with DNA-damaging agents may offer new therapeutic strategies to generally sensitize melanoma toward TRAIL-induced apoptosis.", "isbn" : "1476-5594 (Electronic)$\\backslash$r0950-9232 (Linking)", "pmid" : "18978816", "issn" : "14765594", "doi" : "10.1038/onc.2008.397", "bibtexKey": "Thayaparasingham2009" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/269f3797ff4ac1b93a577872a058e3b6a/pumaizi", "tags" : [ "2009","olayioye","izi","hausser" ], "intraHash" : "69f3797ff4ac1b93a577872a058e3b6a", "interHash" : "b074fdeda801decace7e5763afc90833", "label" : "Heterologous expression of the lipid transfer protein CERT increases therapeutic protein productivity of mammalian 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 Biotechnology", "year": "2009", "url": "https://www.ncbi.nlm.nih.gov/pubmed/19428735", "author": [ "Lore Florin","Antje Pegel","Eric Becker","Angelika Hausser","Monilola A. Olayioye","Hitto Kaufmann" ], "authors": [ {"first" : "Lore", "last" : "Florin"}, {"first" : "Antje", "last" : "Pegel"}, {"first" : "Eric", "last" : "Becker"}, {"first" : "Angelika", "last" : "Hausser"}, {"first" : "Monilola A.", "last" : "Olayioye"}, {"first" : "Hitto", "last" : "Kaufmann"} ], "volume": "141","number": "1-2","pages": "84--90","abstract": "Recent studies have demonstrated that the introduction of transgenes regulating protein transport or affecting post-translational modifications can further improve industrial processes for the production of therapeutic proteins in mammalian cells. Our study on improving therapeutic protein production in CHO cells by heterologous expression of the ceramide transfer protein (CERT) was initiated by the recent discovery that CERT is involved in protein kinase D (PKD)-dependent protein transport from the Golgi to the plasma membrane. We generated a set of CHO DG44 cell lines by stable integration of constructs expressing either CERT wild-type or CERT S132A, a mutant conferring increased lipid transfer activity, or a mock plasmid. CHO cells expressing heterologous CERT demonstrated significantly higher specific productivities of the therapeutic protein HSA when grown in inoculum suspension cultures. This effect translated into significantly increased overall HSA titers in a fed-batch format where cells are grown in chemically defined serum-free media. Furthermore, we could show that CERT also enhanced monoclonal antibody secretion in two IgG production cell lines with different basal productivities. The data demonstrate the potential of CERT engineering to improve mammalian cell culture production processes to yield high amounts of a therapeutic protein product of desired quality. To our knowledge, this is the first study showing a bottle neck in recombinant protein secretion at the Golgi complex in mammalian cells. © 2009 Elsevier B.V. All rights reserved.", "isbn" : "1873-4863 (Electronic)$\\backslash$n0168-1656 (Linking)", "pmid" : "19428735", "issn" : "01681656", "doi" : "10.1016/j.jbiotec.2009.02.014", "bibtexKey": "Florin2009" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2b29b60a76a405d09fe91bb6800068c3e/pumaizi", "tags" : [ "2009","izi","pfizenmaier","kontermann" ], "intraHash" : "b29b60a76a405d09fe91bb6800068c3e", "interHash" : "6dc8db255c76938eeb8e2c8f30756cf1", "label" : "Targeted lipid-coated nanoparticles: Delivery of tumor necrosis factor-functionalized particles to tumor 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 Controlled Release", "year": "2009", "url": "https://www.ncbi.nlm.nih.gov/pubmed/19306900", "author": [ "Sylvia K.E. Messerschmidt","Anna Musyanovych","Martin Altvater","Peter Scheurich","Klaus Pfizenmaier","Katharina Landfester","Roland E. Kontermann" ], "authors": [ {"first" : "Sylvia K.E.", "last" : "Messerschmidt"}, {"first" : "Anna", "last" : "Musyanovych"}, {"first" : "Martin", "last" : "Altvater"}, {"first" : "Peter", "last" : "Scheurich"}, {"first" : "Klaus", "last" : "Pfizenmaier"}, {"first" : "Katharina", "last" : "Landfester"}, {"first" : "Roland E.", "last" : "Kontermann"} ], "volume": "137","number": "1","pages": "69--77","abstract": "Polymeric nanoparticles displaying tumor necrosis factor on their surface (TNF nanocytes) are useful carrier systems capable of mimicking the bioactivity of membrane-bound TNF. Thus, TNF nanocytes are potent activators of TNF receptor 1 and 2 leading to a striking enhancement of apoptosis. However, in vivo applications are hampered by potential systemic toxicity. Here, using TNF nanocytes as a model system, we developed a procedure to generate targeted lipid-coated particles (TLP) in which TNF activity is shielded. The TLPs generated here are composed of an inner single-chain TNF (scTNF)-functionalized, polymeric nanoparticle core surrounded by a lipid coat endowed with polyethylene glycol (PEG) for sterical stabilization and a single-chain Fv (scFv) fragment for targeting. Using a scFv directed against the tumor stroma marker fibroblast activation protein (FAP) we show that TLP and scTNF-TLP specifically bind to FAP-expressing, but not to FAP-negative cells. Lipid coating strongly reduced nonspecific binding of particles and scTNF-mediated cytotoxicity towards FAP-negative cells. In contrast, an increased cytotoxicity of TLP was observed for FAP-positive cells. Thus, through liposome encapsulation, nanoparticles carrying bioactive molecules, which are subject to nonselective uptake and activity towards various cells and tissues, can be converted into target cell-specific composite particles exhibiting a selective activity towards antigen-positive target cells. Besides safe and targeted delivery of death ligands such as TNF, TLP should be suitable for various diagnostic and therapeutic applications, which benefit from a targeted delivery of reagents embedded into the particle core or displayed on the core particle surface. © 2009 Elsevier B.V. All rights reserved.", "isbn" : "1873-4995 (Electronic)$\\backslash$r0168-3659 (Linking)", "pmid" : "19306900", "issn" : "01683659", "doi" : "10.1016/j.jconrel.2009.03.010", "bibtexKey": "Messerschmidt2009" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/258085894ac754f3c12110d4e64881fe7/pumaizi", "tags" : [ "2009","sauter","izi","kulms" ], "intraHash" : "58085894ac754f3c12110d4e64881fe7", "interHash" : "f1e0cb792d50844b31aa37ebf2cf9cfd", "label" : "Mechanism of PP2A-mediated IKKβ dephosphorylation: A systems biological approach", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "BMC Systems Biology", "year": "2009", "url": "https://www.ncbi.nlm.nih.gov/pubmed/19607706", "author": [ "Johannes Witt","Sandra Barisic","Eva Schumann","Frank Allgöwer","Oliver Sawodny","Thomas Sauter","Dagmar Kulms" ], "authors": [ {"first" : "Johannes", "last" : "Witt"}, {"first" : "Sandra", "last" : "Barisic"}, {"first" : "Eva", "last" : "Schumann"}, {"first" : "Frank", "last" : "Allgöwer"}, {"first" : "Oliver", "last" : "Sawodny"}, {"first" : "Thomas", "last" : "Sauter"}, {"first" : "Dagmar", "last" : "Kulms"} ], "volume": "3","pages": "71","abstract": "BACKGROUND: Biological effects of nuclear factor-kappaB (NF kappaB) can differ tremendously depending on the cellular context. For example, NF kappaB induced by interleukin-1 (IL-1) is converted from an inhibitor of death receptor induced apoptosis into a promoter of ultraviolet-B radiation (UVB)-induced apoptosis. This conversion requires prolonged NF kappaB activation and is facilitated by IL-1 + UVB-induced abrogation of the negative feedback loop for NF kappaB, involving a lack of inhibitor of kappaB (I kappaB alpha) protein reappearance. Permanent activation of the upstream kinase IKK beta results from UVB-induced inhibition of the catalytic subunit of Ser-Thr phosphatase PP2A (PP2Ac), leading to immediate phosphorylation and degradation of newly synthesized I kappaB alpha.$\\backslash$n$\\backslash$nRESULTS: To investigate the mechanism underlying the general PP2A-mediated tuning of IKK beta phosphorylation upon IL-1 stimulation, we have developed a strictly reduced mathematical model based on ordinary differential equations which includes the essential processes concerning the IL-1 receptor, IKK beta and PP2A. Combining experimental and modelling approaches we demonstrate that constitutively active, but not post-stimulation activated PP2A, tunes out IKK beta phosphorylation thus allowing for I kappaB alpha resynthesis in response to IL-1. Identifiability analysis and determination of confidence intervals reveal that the model allows reliable predictions regarding the dynamics of PP2A deactivation and IKK beta phosphorylation. Additionally, scenario analysis is used to scrutinize several hypotheses regarding the mode of UVB-induced PP2Ac inhibition. The model suggests that down regulation of PP2Ac activity, which results in prevention of I kappaB alpha reappearance, is not a direct UVB action but requires instrumentality.$\\backslash$n$\\backslash$nCONCLUSION: The model developed here can be used as a reliable building block of larger NF kappa B models and offers comprehensive simplification potential for future modeling of NF kappa B signaling. It gives more insight into the newly discovered mechanisms for IKK deactivation and allows for substantiated predictions and investigation of different hypotheses. The evidence of constitutive activity of PP2Ac at the IKK complex provides new insights into the feedback regulation of NF kappa B, which is crucial for the development of new anti-cancer strategies.", "isbn" : "10.1186/1752-0509-3-71", "pmid" : "19607706", "issn" : "17520509", "doi" : "10.1186/1752-0509-3-71", "bibtexKey": "Witt2009" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2906431f3a1b279de70071885ccfb9fc6/pumaizi", "tags" : [ "2009","izi","hausser" ], "intraHash" : "906431f3a1b279de70071885ccfb9fc6", "interHash" : "fb55fe395a2ecf6b3acd68e13a415671", "label" : "Mitochondrial diacylglycerol initiates protein-kinase-D1-mediated ROS signaling", "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 Science", "year": "2009", "url": "http://jcs.biologists.org/cgi/doi/10.1242/jcs.041061", "author": [ "C. F. Cowell","H. Doppler","I. K. Yan","A. Hausser","Y. Umezawa","P. Storz" ], "authors": [ {"first" : "C. F.", "last" : "Cowell"}, {"first" : "H.", "last" : "Doppler"}, {"first" : "I. K.", "last" : "Yan"}, {"first" : "A.", "last" : "Hausser"}, {"first" : "Y.", "last" : "Umezawa"}, {"first" : "P.", "last" : "Storz"} ], "volume": "122","number": "7","pages": "919--928","abstract": "Increases in reactive oxygen species (ROS) have been implicated in age-related diseases, including cancer. The serine/threonine kinase protein kinase D1 (PKD1) is a stress-responsive kinase and sensor for reactive oxygen species, which can initiate cell survival through NF-kappaB signaling. We have previously shown that in response to ROS, PKD1 is activated at the mitochondria. However, the initial signaling events leading to localization of PKD1 to the mitochondria are unknown. Here, we show that formation of mitochondrial diacylglycerol (DAG) and its binding to PKD1 is the means by which PKD1 is localized to the mitochondria in response to ROS. Interestingly, DAG to which PKD1 is recruited in this pathway is formed downstream of phospholipase D1 (PLD1) and a lipase-inactive PLD1 or inhibition of PLD1 by pharmacological inhibitors blocked PKD1 activation under oxidative stress. To date it has been viewed that monosaturated and saturated DAG formed via PLD1 have no signaling function. However, our data describe a role for PLD1-induced DAG as a competent second messenger at the mitochondria that relays ROS to PKD1-mediated mitochondria-to-nucleus signaling.", "isbn" : "0021-9533 (Print)$\\backslash$r0021-9533 (Linking)", "pmid" : "19258390", "issn" : "0021-9533", "doi" : "10.1242/jcs.041061", "bibtexKey": "Cowell2009" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2c4cd3cc534f35c4950a012d371fed63a/pumaizi", "tags" : [ "2009","izi","kontermann" ], "intraHash" : "c4cd3cc534f35c4950a012d371fed63a", "interHash" : "66b07e67423d40c8b7eb19f1d8934391", "label" : "Strategies to extend plasma half-lives of recombinant antibodies", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "BioDrugs", "year": "2009", "url": "https://www.ncbi.nlm.nih.gov/pubmed/19489651", "author": [ "Roland E. Kontermann" ], "authors": [ {"first" : "Roland E.", "last" : "Kontermann"} ], "volume": "23","number": "2","pages": "93--109","abstract": "Recombinant antibodies, including whole antibodies, antibody fragments, antibody fusion proteins or conjugates, and more recently also small antibody mimetics, have found increasing applications as therapeutics, e.g. for the treatment of cancer or inflammatory diseases. While whole antibodies have an exceptionally long half-life, small antibody derivatives often suffer from rapid elimination from the circulation. In order to improve administration and therapeutic efficacy, modifications to extend the plasma half-life have been developed and implemented in these antibody formats. This review provides a comprehensive summary of the various strategies currently available to extend plasma half-lives of recombinant antibodies.", "isbn" : "1173-8804 (Print)$\\backslash$n1173-8804 (Linking)", "pmid" : "19489651", "issn" : "11738804", "doi" : "10.2165/00063030-200923020-00003", "bibtexKey": "Kontermann2009" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/226314f0e69921730b0efc97115b55a40/pumaizi", "tags" : [ "2009","izi","hausser" ], "intraHash" : "26314f0e69921730b0efc97115b55a40", "interHash" : "f89ba8da040830530be5aa8b5b817b07", "label" : "MODELING COFILIN MEDIATED REGULATION OF CELL MIGRATION AS A BIOCHEMICAL TWO-INPUT SWITCH", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 7, "pub-type": "inproceedings", "booktitle": "Proc.of the 3rd Foundations of Systems Biology in Engineering (FOSBE)", "year": "2009", "url": "https://lirias.kuleuven.be/bitstream/123456789/568203/1/BreindlWal2009.pdf", "author": [ "Christian Breindl","Steffen Waldherr","Angelika Hausser","Frank Allgöwer" ], "authors": [ {"first" : "Christian", "last" : "Breindl"}, {"first" : "Steffen", "last" : "Waldherr"}, {"first" : "Angelika", "last" : "Hausser"}, {"first" : "Frank", "last" : "Allgöwer"} ], "pages": "60--63","abstract": "Cell migration plays an essential role in many physiological processes such as embryogenesis, immune response, and wound healing. However, increased cell motility also contributes to invasion and metastases of tumor cells. Therefore, understanding the intracellular mechanisms which regulate cell migration is an important issue. In this paper a mathematical model describing the regulation of cofilin, which is a direct regulator of cell motility, is developed. The mathematical model is used to study the effects of different signaling stimuli on cofilin activity. In particular, the model analysis predicts that cell migration can be stopped reliably by a specific combined stimulation of the cofilin regulatory network. This hypothesis thus proposes a mechanism how cells may sustainably be kept at a fixed place without much signaling effort.", "bibtexKey": "Breindl2009" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2e8bdf9070389ea04a3b58176c53feba3/pumaizi", "tags" : [ "2009","olayioye","izi" ], "intraHash" : "e8bdf9070389ea04a3b58176c53feba3", "interHash" : "4759b658b300e6b5bf8817146cfa4d7f", "label" : "DLC1 activation requires lipid interaction through a polybasic region preceding the RhoGAP domain.", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Molecular biology of the cell", "year": "2009", "url": "https://www.ncbi.nlm.nih.gov/pubmed/19710422", "author": [ "Patrik Erlmann","Simone Schmid","Florian A Horenkamp","Matthias Geyer","Thomas G Pomorski","Monilola A Olayioye" ], "authors": [ {"first" : "Patrik", "last" : "Erlmann"}, {"first" : "Simone", "last" : "Schmid"}, {"first" : "Florian A", "last" : "Horenkamp"}, {"first" : "Matthias", "last" : "Geyer"}, {"first" : "Thomas G", "last" : "Pomorski"}, {"first" : "Monilola A", "last" : "Olayioye"} ], "volume": "20","number": "20","pages": "4400--4411","abstract": "Deleted in Liver Cancer 1 (DLC1) is a GTPase-activating protein (GAP) with specificity for RhoA, RhoB, and RhoC that is frequently deleted in various tumor types. By inactivating these small GTPases, DLC1 controls actin cytoskeletal remodeling and biological processes such as cell migration and proliferation. Here we provide evidence that DLC1 binds to phosphatidylinositol-4,5-bisphosphate (PI(4,5)P(2)) through a previously unrecognized polybasic region (PBR) adjacent to its RhoGAP domain. Importantly, PI(4,5)P(2)-containing membranes are shown to stimulate DLC1 GAP activity in vitro. In living cells, a DLC1 mutant lacking an intact PBR inactivated Rho signaling less efficiently and was severely compromised in suppressing cell spreading, directed migration, and proliferation. We therefore propose that PI(4,5)P(2) is an important cofactor in DLC1 regulation in vivo and that the PBR is essential for the cellular functions of the protein.", "isbn" : "1939-4586 (Electronic)$\\backslash$r1059-1524 (Linking)", "pmid" : "19710422", "issn" : "1059-1524", "doi" : "10.1091/mbc.E09-03-0247", "bibtexKey": "Erlmann2009" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2f7383c3bc2dd356bff255fdaa81346fe/pumaizi", "tags" : [ "2009","olayioye","izi","pfizenmaier","hausser" ], "intraHash" : "f7383c3bc2dd356bff255fdaa81346fe", "interHash" : "899b90261afe6ea641eeabaf54e93072", "label" : "Protein kinase D regulates cell migration by direct phosphorylation of the cofilin phosphatase slingshot 1 like", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Cancer Research", "year": "2009", "url": "https://doi.org/10.1158/0008-5472.CAN-09-0718", "author": [ "Philipp Peterburs","Johanna Heering","Gisela Link","Klaus Pfizenmaier","Monilola A. Olayioye","Angelika Hausser" ], "authors": [ {"first" : "Philipp", "last" : "Peterburs"}, {"first" : "Johanna", "last" : "Heering"}, {"first" : "Gisela", "last" : "Link"}, {"first" : "Klaus", "last" : "Pfizenmaier"}, {"first" : "Monilola A.", "last" : "Olayioye"}, {"first" : "Angelika", "last" : "Hausser"} ], "volume": "69","number": "14","pages": "5634--5638","abstract": "Protein kinase D (PKD) has been identified as a negative regulator of epithelial cell migration; however, its molecular substrates and downstream signaling pathways that mediate this activity have remained elusive. In this study, we provide evidence that the cofilin phosphatase slingshot 1 like (SSH1L), an important regulator of the complex actin remodeling machinery, is a novel in vivo PKD substrate. PKD-mediated phosphorylation of serines 937 and 978 regulates SSH1L subcellular localization by binding of 14-3-3 proteins and thus impacts the control of local cofilin activation and actin remodeling during cell migration. In line with this, we show that the loss of PKD decreases cofilin phosphorylation, induces a more spread cell morphology, and stimulates chemotactic migration of breast cancer cells in an SSHL1-dependent fashion. Our data thus identify PKD as a central regulator of the cofilin signaling network via direct phosphorylation and regulation of SSH1L.", "isbn" : "1538-7445 (Electronic)$\\backslash$r0008-5472 (Linking)", "pmid" : "19567672", "issn" : "00085472", "doi" : "10.1158/0008-5472.CAN-09-0718", "bibtexKey": "Peterburs2009" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2fb8ce96199c629bca215d6f0d71aa3b9/pumaizi", "tags" : [ "2009","izi","pfizenmaier","hausser" ], "intraHash" : "fb8ce96199c629bca215d6f0d71aa3b9", "interHash" : "b77ee765db2cc3305eac6b30cadd460b", "label" : "A Golgi PKD activity reporter reveals a crucial role of PKD in nocodazole-induced Golgi dispersal", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Traffic", "year": "2009", "url": "https://www.ncbi.nlm.nih.gov/pubmed/19416469", "author": [ "Yannick F. Fuchs","Stephan A. Eisler","Gisela Link","Oliver Schlicker","Gertrude Bunt","Klaus Pfizenmaier","Angelika Hausser" ], "authors": [ {"first" : "Yannick F.", "last" : "Fuchs"}, {"first" : "Stephan A.", "last" : "Eisler"}, {"first" : "Gisela", "last" : "Link"}, {"first" : "Oliver", "last" : "Schlicker"}, {"first" : "Gertrude", "last" : "Bunt"}, {"first" : "Klaus", "last" : "Pfizenmaier"}, {"first" : "Angelika", "last" : "Hausser"} ], "volume": "10","number": "7","pages": "858--867","abstract": "The protein kinase D (PKD) family comprises multifunctional serine/threonine-specific protein kinases with three mammalian isoforms: PKD1, PKD2 and PKD3. A prominent PKD function is the regulation of basolateral-targeted transport carrier fission from the trans-Golgi network (TGN). To visualize site-specific PKD activation at this organelle, we designed a molecular reporter consisting of a PKD-specific substrate sequence fused to enhanced green fluorescent protein (EGFP), specifically targeted to the TGN via the p230 GRIP domain. Quantitative analyses using a phosphospecific antibody and ratiometric fluorescence imaging revealed that Golgi-specific phosphorylation of the reporter was strictly dependent on stimulation of endogenous PKD or transient expression of active PKD constructs. Conversely, PKD-specific pharmacological inhibitors and siRNA-mediated PKD knockdown suppressed reporter phosphorylation. Using this reporter we investigated a potential role for PKD in the regulation of Golgi complex morphology. Interestingly, nocodazole-induced Golgi complex break-up and dispersal was associated with local PKD activation as measured by reporter phosphorylation and this was efficiently blocked by expression of a dominant-negative PKD mutant or PKD depletion. Our data thus identify a novel link between PKD activity and the microtubule cytoskeleton, whereby Golgi complex integrity is regulated.", "isbn" : "1600-0854 (Electronic)$\\backslash$r1398-9219 (Linking)", "pmid" : "19416469", "issn" : "13989219", "doi" : "10.1111/j.1600-0854.2009.00918.x", "bibtexKey": "Fuchs2009" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/27b9d02641f9bd10f1033b420cb527c1c/pumaizi", "tags" : [ "2009","izi","pfizenmaier" ], "intraHash" : "7b9d02641f9bd10f1033b420cb527c1c", "interHash" : "432b74883ac21610a2d565d465a5943f", "label" : "Improving TNF as a cancer therapeutic: Tailor-made TNF fusion proteins with conserved antitumor activity and reduced systemic side effects", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "BioFactors", "year": "2009", "url": "https://www.ncbi.nlm.nih.gov/pubmed/19484741", "author": [ "Jeannette Gerspach","Klaus Pfizenmaier","Harald Wajant" ], "authors": [ {"first" : "Jeannette", "last" : "Gerspach"}, {"first" : "Klaus", "last" : "Pfizenmaier"}, {"first" : "Harald", "last" : "Wajant"} ], "volume": "35","number": "4","pages": "364--372","abstract": "Tumor necrosis factor (TNF) is highly pleiotropic cytokine regulating diverse cellular processes such as proliferation, cell migration, angiogenesis, differentiation, apoptosis, necrosis, but also survival. Because of its name-giving tumor necrosis-inducing capabilities, TNF has attracted attention very early for antitumor therapy. Although TNF is in clinical use for treatment of soft tissue sarcoma in isolated limb perfusion, its broad use in tumor therapy is prevented so far by its strong systemic proinflammatory effects. Nevertheless, over the past decade, a variety of tailor-made TNF variants have been developed with the aim to reduce TNFs systemic activity without losing its antitumoral effects. Here, we review the progress made toward improving the efficacy of TNF by genetic engineering, tumor targeting, and introduction of prodrug concepts.", "isbn" : "1872-8081 (Electronic)\n0951-6433 (Linking)", "pmid" : "19484741", "issn" : "09516433", "doi" : "10.1002/biof.50", "bibtexKey": "Gerspach2009" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2391bd7e9d75d8129fe83ce63070a501c/pumaizi", "tags" : [ "2009","izi","pfizenmaier","kontermann" ], "intraHash" : "391bd7e9d75d8129fe83ce63070a501c", "interHash" : "e06f5336fe7e1accef43232cd1e1cd12", "label" : "Antagonists of TNF action: clinical experience and new developments", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Expert Opinion on Drug Discovery", "year": "2009", "url": "http://www.tandfonline.com/doi/full/10.1517/17460440902785167", "author": [ "Roland E Kontermann","Peter Scheurich","Klaus Pfizenmaier" ], "authors": [ {"first" : "Roland E", "last" : "Kontermann"}, {"first" : "Peter", "last" : "Scheurich"}, {"first" : "Klaus", "last" : "Pfizenmaier"} ], "volume": "4","number": "3","pages": "279--292","abstract": "BACKGROUND: TNF is a central mediator of inflammation and key target for intervention in inflammatory diseases such as rheumatoid arthritis, psoriasis and Crohn's disease. The four at present approved protein therapeutics directly target TNF and inhibit binding to its two TNF receptors. Treatment with TNF antagonists results in significant clinical responses and is generally well tolerated. OBJECTIVE: Ten years of clinical experience with 1 million patients treated also revealed the limits of the available antagonists and potential therapy-associated risks, foremost being tuberculosis reactivation, but also neurologic and hematologic events, and even malignancies. These findings ask for improvement of established therapies. METHOD: We here review published literature on strategies interfering with TNF action and provide an overview of the now approved antagonists of TNF action as well as new reagents under development. CONCLUSION: Clinical experience with approved TNF antagonists shows that there is a demand for minimizing risks associated with persistent blocking of TNF action. With new TNF pathway-targeting reagents and new concepts based on receptor-selective intervention under development, it is foreseeable that efficacy and safety will be further improved and that TNF-targeting strategies will be exploited in further inflammatory and other diseases, including metabolic diseases and cancer.", "isbn" : "1746044090278", "pmid" : "23489126", "issn" : "1746-0441", "doi" : "10.1517/17460440902785167", "bibtexKey": "Kontermann2009a" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2f06bc61a38765191a52c1de5b1a17e5f/pumaizi", "tags" : [ "2009","izi","pfizenmaier" ], "intraHash" : "f06bc61a38765191a52c1de5b1a17e5f", "interHash" : "dbdc7807feae383389862b3fd703c1c0", "label" : "Trimer Stabilization, Oligomerization, and Antibody-Mediated Cell Surface Immobilization Improve the Activity of Soluble Trimers of CD27L, CD40L, 41BBL, and Glucocorticoid-Induced TNF Receptor Ligand", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "The Journal of Immunology", "year": "2009", "url": "http://www.jimmunol.org/cgi/doi/10.4049/jimmunol.0802597", "author": [ "A. Wyzgol","N. Muller","A. Fick","S. Munkel","G. U. Grigoleit","K. Pfizenmaier","H. Wajant" ], "authors": [ {"first" : "A.", "last" : "Wyzgol"}, {"first" : "N.", "last" : "Muller"}, {"first" : "A.", "last" : "Fick"}, {"first" : "S.", "last" : "Munkel"}, {"first" : "G. U.", "last" : "Grigoleit"}, {"first" : "K.", "last" : "Pfizenmaier"}, {"first" : "H.", "last" : "Wajant"} ], "volume": "183","number": "3","pages": "1851--1861","abstract": "For many ligands of the TNF family, trimer stability and oligomerization status are crucial determinants of receptor activation. However, for the immunostimulatory ligands CD27L, CD40L, 41BBL, and glucocorticoid-induced TNF receptor ligand (GITRL) detailed information regarding these requirements is lacking. Here, we comprehensively evaluated the effect of trimer stability and oligomerization on receptor activation by these ligands. Treatment with soluble Flag-tagged CD27L, 41BBL, and GITRL minimally activated receptor signaling, while Flag-CD40L was highly active. Oligomerization with anti-Flag Abs further enhanced the specific activity of Flag-CD40L 10-fold and of Flag-41BBL more than 200-fold, but it failed to activate Flag-CD27L and Flag-GITRL. We next investigated the relevance of trimer stability by introducing the tenascin-C (TNC) trimerization domain, yielding stabilized Flag-TNC-ligand trimers. Oligomerization with anti-Flag Ab potently activated signaling by Flag-TNC-CD27L and Flag-TNC-GITRL and, albeit to a lesser extent, Flag-TNC-CD40L and Flag-TNC-41BBL. Forced hexamerization, by introducing an Ig Fc domain, revealed that hexameric derivatives of Flag-TNC-41BBL, Flag-CD40L, and Flag-TNC-GITRL all activate receptor signaling with high efficiency, whereas hexameric Flag-CD27L variant left inactive. Finally, we attempted to selectively activate receptor signaling on targeted cells, by using Ab fragment (single-chain fragment variable region, scFv)-ligand fusion proteins, an approach previously applied to other TNF ligands. Target cell surface Ag-selective activation was achieved for scFv-41BBL, scFv-CD40L, and scFv-GITRL, although the latter two displayed already significant activity toward Ag-negative cells. In conclusion, our data establish that trimeric CD40L is active, 41BBL requires hexamerization, GITRL requires trimer stabilization, and CD27L requires trimer stabilization and oligomerization. Furthermore, surface immobilization might be exploited to gain locally enhanced ligand activity.", "isbn" : "1550-6606 (Electronic)$\\backslash$r0022-1767 (Linking)", "pmid" : "19596991", "issn" : "0022-1767", "doi" : "10.4049/jimmunol.0802597", "bibtexKey": "Wyzgol2009" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2e2d80fa424a48562f954906260cd748c/pumaizi", "tags" : [ "2009","izi","scheuric" ], "intraHash" : "e2d80fa424a48562f954906260cd748c", "interHash" : "1438ea99c89c7d2994771791c9a79f80", "label" : "ON/OFF and beyond - A Boolean model of apoptosis", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 5, "pub-type": "article", "journal": "PLoS Computational Biology", "year": "2009", "url": "https://www.ncbi.nlm.nih.gov/pubmed/20011108", "author": [ "Rebekka Schlatter","Kathrin Schmich","Ima Avalos Vizcarra","Peter Scheurich","Thomas Sauter","Christoph Borner","Michael Ederer","Irmgard Merfort","Oliver Sawodny" ], "authors": [ {"first" : "Rebekka", "last" : "Schlatter"}, {"first" : "Kathrin", "last" : "Schmich"}, {"first" : "Ima Avalos", "last" : "Vizcarra"}, {"first" : "Peter", "last" : "Scheurich"}, {"first" : "Thomas", "last" : "Sauter"}, {"first" : "Christoph", "last" : "Borner"}, {"first" : "Michael", "last" : "Ederer"}, {"first" : "Irmgard", "last" : "Merfort"}, {"first" : "Oliver", "last" : "Sawodny"} ], "volume": "5","number": "12","pages": "e1000595","abstract": "Apoptosis is regulated by several signaling pathways which are extensively linked by crosstalks. Boolean or logical modeling has become a promising approach to capture the qualitative behavior of such complex networks. Here we built a large-scale literature-based Boolean model of the central intrinsic and extrinsic apoptosis pathways as well as pathways connected with them. The model responds to several external stimuli such as Fas ligand, TNF-alpha, UV-B irradiation, interleukin-1beta and insulin. Timescales and multi-value node logic were used and turned out to be indispensable to reproduce the behavior of the apoptotic network. The coherence of the model was experimentally validated. Thereby an UV-B dose-effect is shown for the first time in mouse hepatocytes. Analysis of the model revealed a tight regulation emerging from high connectivity and spanning crosstalks and a particular importance of feedback loops. An unexpected feedback from Smac release to RIP could further increase complex II formation. The introduced Boolean model provides a comprehensive and coherent description of the apoptosis network behavior. It gives new insights into the complex interplay of pro- and antiapoptotic factors and can be easily expanded to other signaling pathways.", "isbn" : "1553-7358 (Electronic)$\\backslash$n1553-734X (Linking)", "pmid" : "20011108", "issn" : "1553734X", "doi" : "10.1371/journal.pcbi.1000595", "bibtexKey": "Schlatter2009" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/223d0dcdf6bae68be471aa50045bd9df2/pumaizi", "tags" : [ "2009","izi","kontermann" ], "intraHash" : "23d0dcdf6bae68be471aa50045bd9df2", "interHash" : "cd27562eddac9234360123e4c9c67caf", "label" : "Biodistribution of a bispecific single-chain diabody and its half-life extended derivatives", "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": "2009", "url": "https://www.ncbi.nlm.nih.gov/pubmed/19628871", "author": [ "Roland Stork","Emmanuelle Campigna","Bruno Robert","Dafne Müller","Roland E. Kontermann" ], "authors": [ {"first" : "Roland", "last" : "Stork"}, {"first" : "Emmanuelle", "last" : "Campigna"}, {"first" : "Bruno", "last" : "Robert"}, {"first" : "Dafne", "last" : "Müller"}, {"first" : "Roland E.", "last" : "Kontermann"} ], "volume": "284","number": "38","pages": "25612--25619","abstract": "Small recombinant antibody molecules such as bispecific single-chain diabodies (scDb) possessing a molecular mass of approximately 55 kDa are rapidly cleared from circulation. We have recently extended the plasma half-life of scDb applying various strategies including PEGylation, N-glycosylation and fusion to an albumin-binding domain (ABD) from streptococcal protein G. Here, we further analyzed the influence of these modifications on the biodistribution of a scDb directed against carcinoembryonic antigen (CEA) and CD3 capable of retargeting T cells to CEA-expressing tumor cells. We show that a prolonged circulation time results in an increased accumulation in CEA+ tumors, which was most pronounced for scDb-ABD and PEGylated scDb. Interestingly, tumor accumulation of the scDb-ABD fusion protein was approximately 2-fold higher compared with PEGylated scDb, although both molecules exhibit similar plasma half-lives and similar affinities for CEA. Comparing half-lives in neonatal Fc receptor (FcRn) wild-type and FcRn heavy chain knock-out mice the contribution of the FcRn to the long plasma half-life of scDb-ABD was confirmed. The half-life of scDb-ABD was approximately 2-fold lower in the knock-out mice, while no differences were observed for PEGylated scDb. Binding of the scDb derivatives to target and effector cells was not or only marginally affected by the modifications, although, compared with scDb, a reduced cytotoxic activity was observed for scDb-ABD, which was further reduced in the presence of albumin. In summary, these findings demonstrate that the extended half-life of a bispecific scDb translates into improved accumulation in antigen-positive tumors but that modifications might also affect scDb-mediated cytotoxicity.", "isbn" : "4971168567", "pmid" : "19628871", "issn" : "00219258", "doi" : "10.1074/jbc.M109.027078", "bibtexKey": "Stork2009" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/20d859d78e24cdfd30b86c5e0d83f48eb/pumaizi", "tags" : [ "2009","izi","scheuric" ], "intraHash" : "0d859d78e24cdfd30b86c5e0d83f48eb", "interHash" : "3916d943dff4e46b5fbab2ff57c7804a", "label" : "Nanoscale arrangement of apoptotic ligands reveals a demand for a minimal lateral distance for efficient death receptor activation", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Nano Letters", "year": "2009", "url": "https://www.ncbi.nlm.nih.gov/pubmed/19772290", "author": [ "Julia Ranzinger","Anja Krippner-Heidenreich","Tamas Haraszti","Eva Bock","Jessica Tepperink","Joachim P. Spatz","Peter Scheurich" ], "authors": [ {"first" : "Julia", "last" : "Ranzinger"}, {"first" : "Anja", "last" : "Krippner-Heidenreich"}, {"first" : "Tamas", "last" : "Haraszti"}, {"first" : "Eva", "last" : "Bock"}, {"first" : "Jessica", "last" : "Tepperink"}, {"first" : "Joachim P.", "last" : "Spatz"}, {"first" : "Peter", "last" : "Scheurich"} ], "volume": "9","number": "12","pages": "4240--4245","abstract": "Cellular apoptosis, the prototype of programmed cell death, can be induced by activation of so-called death receptors. Interestingly, soluble and membrane-bound members of death receptor ligands can differentially activate their receptors. Using the death receptor ligand tumor necrosis factor (TNF) presented on a surface in a nanoscaled pattern with spacings between 58 and 290 nm, we investigated its requirements for spatial arrangement and motility to efficiently activate TNF receptor (TNFR)1 and TNFR2 as well as its chimeras TNFR1-Fas and TNFR2-Fas. We show that the mere mechanical fixation of TNF is insufficient to efficiently activate TNFR2 that is responsive to only the membrane bound form of TNF but not its soluble form. Rather, an additional stabilization of TNFR2(-Fas) by cluster formation seems to be mandatory for efficient activation. In contrast, TNFR1(-Fas) is strongly activated by TNF spaced within up to 200 nm distances, whereas larger spacings of 290 nm fails completely. Furthermore, unlike for TNFR2(-Fas) no dose-response relationship to increasing distances of nanostructured ligands could be observed for TNFR1-(Fas), suggesting that compartmentalization of the cell membrane in confinement zones of approximately 200 nm regulates TNFR1 activation.", "isbn" : "1530-6984", "pmid" : "19772290", "issn" : "15306984", "doi" : "10.1021/nl902429b", "bibtexKey": "Ranzinger2009" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/2584ec27203b3271527802032b52bcb14/pumaizi", "tags" : [ "2009","izi","pfizenmaier" ], "intraHash" : "584ec27203b3271527802032b52bcb14", "interHash" : "3f9aec0ad24a126af3c921825dd59c7a", "label" : "Death ligands designed to kill: Development and application of targeted cancer therapeutics based on proapoptotic TNF family ligands", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Results and Problems in Cell Differentiation", "year": "2009", "url": "https://www.ncbi.nlm.nih.gov/pubmed/19142623", "author": [ "Jeannette Gerspach","Harald Wajant","Klaus Pfizenmaier" ], "authors": [ {"first" : "Jeannette", "last" : "Gerspach"}, {"first" : "Harald", "last" : "Wajant"}, {"first" : "Klaus", "last" : "Pfizenmaier"} ], "volume": "49","pages": "241--273","abstract": "The identification of molecular markers associated with cancer development or progression, opened a new era in the development of therapeutics. The successful introduction of a few low molecular weight chemicals and recombinant protein therapeutics with targeted actions into clinical practice have raised great expectations to broadly improve cancer therapy with respect to both overall clinical responses and tolerability. Targeting the apoptotic machinery of malignant cells is an attractive concept to combat cancer, which is currently exploited for the proapoptotic members of the TNF ligand family at various stages of preclinical and clinical development. This review summarizes recent progress in this rapidly progressing field of \"biologic\" therapies targeting the death receptors of TNF, CD95L, and TRAIL by means of its cognate protein ligands, receptor specific antibodies, and gene therapeutic approaches. Preclinical data on newly derived variants and fusion proteins based on these death ligands, designed to act in a tumor restricted manner, thereby preventing a systemic, potentially harmful action, will also be discussed.", "isbn" : "0080-1844 (Print)$\\backslash$n0080-1844 (Linking)", "pmid" : "19142623", "issn" : "00801844", "doi" : "10.1007/400_2008_22", "bibtexKey": "Gerspach2009a" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/21ad0abdfa34f60051e142817cc0def4b/pumaizi", "tags" : [ "2009","izi","mueller","kontermann" ], "intraHash" : "1ad0abdfa34f60051e142817cc0def4b", "interHash" : "33f5d9a1d0eb2d8f3bb61290d5a0b433", "label" : "Targeting of Epidermal Growth Factor Receptor (EGFR)-Expressing Tumor Cells with Sterically Stabilized Affibody Liposomes (SAL)", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Bioconjugate Chemistry", "year": "2009", "url": "http://dx.doi.org/10.1021/bc900061v", "author": [ "Julia Beuttler","Miriam Rothdiener","Dafne Müller","Fredrik Y. Frejd","Roland E. Kontermann" ], "authors": [ {"first" : "Julia", "last" : "Beuttler"}, {"first" : "Miriam", "last" : "Rothdiener"}, {"first" : "Dafne", "last" : "Müller"}, {"first" : "Fredrik Y.", "last" : "Frejd"}, {"first" : "Roland E.", "last" : "Kontermann"} ], "volume": "20","number": "6","pages": "1201-1208","abstract": "Affibody molecules are small and stable antigen-binding molecules derived from the B domain of protein A. We applied a bivalent, high-affinity epidermal growth factor receptor (EGFR)-specific affibody molecule for the generation of targeted PEGylated liposomes. These sterically stabilized affibody liposomes (SAL) were produced by chemical coupling of the cysteine-modified affibody molecule to maleimide-PEG2000-DSPE and subsequent insertion into PEGylated liposomes. These SAL showed strong and selective binding to EGFR-expressing tumor cell lines. Binding was dependent on the amount of inserted affibody molecule−lipid conjugates and could be blocked by soluble EGF. Approximately 30\\% of binding activity was still retained after 6 days of incubation in human plasma at 37 °C. Binding of SAL to cells led to efficient internalization of the liposomes. Using mitoxantrone-loaded liposomes, we observed for SAL, compared to untargeted liposomes, an enhanced cytotoxicity toward EGFR-expressing cells. In summary, we show that SAL can be easily prepared from affibody molecules and thus may be suitable for the development of carrier systems for targeted delivery of drugs.", "eprint" : "http://dx.doi.org/10.1021/bc900061v", "doi" : "10.1021/bc900061v", "bibtexKey": "doi:10.1021/bc900061v" } , { "type" : "Publication", "id" : "https://puma.ub.uni-stuttgart.de/bibtex/25a1e019c89adfc15d31fc58663042d1a/pumaizi", "tags" : [ "2009","izi","scheuric" ], "intraHash" : "5a1e019c89adfc15d31fc58663042d1a", "interHash" : "8d5122a4d5c4041ae294d65687d1840b", "label" : "Tumor necrosis factor receptor-associated factor-1 enhances proinflammatory TNF receptor-2 signaling and modifies TNFR1-TNFR2 cooperation", "user" : "pumaizi", "description" : "", "date" : "2025-10-17 10:53:57", "changeDate" : "2025-10-17 10:53:57", "count" : 3, "pub-type": "article", "journal": "Oncogene", "year": "2009", "url": "https://www.ncbi.nlm.nih.gov/pubmed/19287455", "author": [ "A. Wicovsky","F. Henkler","S. Salzmann","P. Scheurich","C. Kneitz","H. Wajant" ], "authors": [ {"first" : "A.", "last" : "Wicovsky"}, {"first" : "F.", "last" : "Henkler"}, {"first" : "S.", "last" : "Salzmann"}, {"first" : "P.", "last" : "Scheurich"}, {"first" : "C.", "last" : "Kneitz"}, {"first" : "H.", "last" : "Wajant"} ], "volume": "28","number": "15","pages": "1769--1781","abstract": "It has been shown that tumor necrosis factor receptor-2 (TNFR2) stimulation leads to degradation of TNF receptor associated factor-2 (TRAF2) and inhibition of TNFR1-induced activation of NFkappaB and JNK. Here, we show that TRAF1 inhibits TNFR2-induced proteasomal degradation of TRAF2 and relieves TNFR1-induced activation of NFkappaB from the inhibitory effect of TNFR2. TRAF1 co-recruited with TRAF2 to both TNF receptors. Despite lacking an amino-terminal RING/zinc-finger domain, TRAF1 did not interfere with TNFR1-induced activation of JNK and NFkappaB. It is noted that physiological expression levels of TRAF1 enhanced NFkappaB activation and interleukin-8 (IL8) production induced by TNFR2. Thus, TRAF1 shifts the quality of integrated TNFR1-TNFR2 signaling from apoptosis induction to proinflammatory NFkappaB signaling.", "isbn" : "1476-5594", "pmid" : "19287455", "issn" : "09509232", "doi" : "10.1038/onc.2009.29", "bibtexKey": "Wicovsky2009" } ] }