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X-linked and cellular IAPs modulate the stability of C-RAF kinase and cell motility

X-linked and cellular IAPs modulate the stability of C-RAF kinase and cell motility

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DOGAN, Taner, Gregory S. HARMS, Mirko HEKMAN, Christiaan KARREMAN, Tripat Kaur OBEROI, Emad S. ALNEMRI, Ulf R. RAPP, Krishnaraj RAJALINGAM, 2008. X-linked and cellular IAPs modulate the stability of C-RAF kinase and cell motility. In: Nature cell biology. 10(12), pp. 1447-1455. ISSN 1465-7392. eISSN 1476-4679

@article{Dogan2008-12X-lin-38710, title={X-linked and cellular IAPs modulate the stability of C-RAF kinase and cell motility}, year={2008}, doi={10.1038/ncb1804}, number={12}, volume={10}, issn={1465-7392}, journal={Nature cell biology}, pages={1447--1455}, author={Dogan, Taner and Harms, Gregory S. and Hekman, Mirko and Karreman, Christiaan and Oberoi, Tripat Kaur and Alnemri, Emad S. and Rapp, Ulf R. and Rajalingam, Krishnaraj}, note={There is an Erratum (January 2009) associated with this Article : Nature Cell Biology 11, 110 (2009), http://dx.doi.org/10.1038/ncb0109-110} }

<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/38710"> <dc:creator>Hekman, Mirko</dc:creator> <dc:contributor>Oberoi, Tripat Kaur</dc:contributor> <dc:contributor>Alnemri, Emad S.</dc:contributor> <dcterms:abstract xml:lang="eng">Inhibitor of apoptosis proteins (IAP) are evolutionarily conserved anti-apoptotic regulators. C-RAF protein kinase is a direct RAS effector protein, which initiates the classical mitogen-activated protein kinase (MAPK) cascade. This signalling cascade mediates diverse biological functions, such as cell growth, proliferation, migration, differentiation and survival. Here we demonstrate that XIAP and c-IAPs bind directly to C-RAF kinase and that siRNA-mediated silencing of XIAP and c-IAPs leads to stabilization of C-RAF in human cells. XIAP binds strongly to C-RAF and promotes the ubiquitylation of C-RAF in vivo through the Hsp90-mediated quality control system, independently of its E3 ligase activity. In addition, XIAP or c-IAP-1/2 knockdown cells showed enhanced cell migration in a C-RAF-dependent manner. XIAP promotes binding of CHIP (carboxy terminal Hsc70-interacting protein), a chaperone-associated ubiquitin ligase, to the C-RAF-Hsp90 complex in vivo. Interfering with CHIP expression resulted in stabilization of C-RAF and enhanced cell migration, as observed in XIAP knockdown cells. Our data show an unexpected role of XIAP and c-IAPs in the turnover of C-RAF protein, thereby modulating the MAPK signalling pathway and cell migration.</dcterms:abstract> <dc:contributor>Harms, Gregory S.</dc:contributor> <dc:contributor>Hekman, Mirko</dc:contributor> <dc:creator>Karreman, Christiaan</dc:creator> <dc:creator>Alnemri, Emad S.</dc:creator> <dc:contributor>Dogan, Taner</dc:contributor> <dc:contributor>Rajalingam, Krishnaraj</dc:contributor> <dcterms:issued>2008-12</dcterms:issued> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2017-05-04T07:30:05Z</dcterms:available> <dc:creator>Rajalingam, Krishnaraj</dc:creator> <dcterms:title>X-linked and cellular IAPs modulate the stability of C-RAF kinase and cell motility</dcterms:title> <dc:creator>Oberoi, Tripat Kaur</dc:creator> <dc:creator>Harms, Gregory S.</dc:creator> <dc:contributor>Karreman, Christiaan</dc:contributor> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2017-05-04T07:30:05Z</dc:date> <dc:creator>Dogan, Taner</dc:creator> <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/38710"/> <dc:contributor>Rapp, Ulf R.</dc:contributor> <dc:language>eng</dc:language> <dc:creator>Rapp, Ulf R.</dc:creator> </rdf:Description> </rdf:RDF>

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