Proteomic characterization of ubiquitin-dependent processes in the secretory pathway

点击翻译按钮获取中文摘要

This research proposal aims at characterizing non-proteolytic functions of the ubiquitin system that are involved in maintaining homeostasis in the secretory pathway. To this end we plan to purify mem-brane-associated Cdc48 containing protein complexes and identify their functions by genetic and biochemical methods. The AAAATPase Cdc48, in mammals termed p97 or “valosin containing protein” (VCP), is a key player in many ubiquitin-dependent processes like homeotypic membrane fusion, cell cycle control, proteasome-mediated protein degradation and DNA repair. To fulfill these activities, Cdc48/p97 teams up with a large set of diverse ancillary proteins in a temporally and spatially con-trolled manner. Notably, the vast majority of the presently known Cdc48/p97 co-factors contain ubiquitin binding domains or are elsewise linked to the ubiquitin system. However, in most cases we lack in depth knowledge on their molecular function. In the course of this work we plan to isolate novel Cdc48 interacting proteins, determine their function and establish a network of Cdc48 co-factors that integrates this versatile enzyme into particular ubiquitin-dependent processes in the secretory pathway.