Investigation of the interaction of FAT10 and VCP (p97)


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SCHWAB, Ricarda, 2015. Investigation of the interaction of FAT10 and VCP (p97)

@phdthesis{Schwab2015Inves-32087, title={Investigation of the interaction of FAT10 and VCP (p97)}, year={2015}, author={Schwab, Ricarda}, address={Konstanz}, school={Universität Konstanz} }

Investigation of the interaction of FAT10 and VCP (p97) In the present study the interaction of the ubiquitin-like modifier HLA-F adjacent transcript 10 (FAT10) with the putative substrate Valosin-containing protein (VCP) was investigated. VCP is a hexameric ATPase associated with various activities (AAA) and extracts proteins from the Endoplasmic Reticulum (ER) membrane or from protein complexes. In this function as a segregase VCP is involved in different ubiquitin-dependent processes reaching from the ER associated degradation (ERAD) and cell cycle regulation to membrane fusion events.<br />In addition to a minor covalent attachment of FAT10 to VCP, which led to the degradation of the VCP-FAT10 conjugate by the proteasome, the more prominent non-covalent interaction of both proteins was examined in more detail and the functional consequences arising out of it. It was shown that FAT10 and VCP interact under endogenous conditions and further in vitro experiments revealed that they interact directly. Treatment with the VCP specific inhibitor Eeyarestatin I or use of an ATPase dead VCP mutant didn’t alter the degradation rate of bulk FAT10 conjugates, whereas treatment with the inhibitor DBeQ increased the degradation rate of the FAT10 conjugates. Furthermore the effect of FAT10 on VCP function was studied. Neither the hexamer stability nor the ATPase activity of VCP was influenced by FAT10. Only a difference in the degradation of the ERAD model substrate a1-Antitrypsin was observed in preliminary experiments. Taken all results together it can be concluded that the consequences of the VCP-FAT10 interaction are different to consequences arising from the interaction of VCP with ubiquitin, and that the FAT10-VCP interaction might play a specific role in the immune system or during inflammatory processes when FAT10 is highly up-regulated. eng 2015-11-09T11:57:26Z Schwab, Ricarda 2015-11-09T11:57:26Z Schwab, Ricarda 2015

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