Endoplasmic reticulum di-glycine modified proteome under p97/VCP inhibition

ABSTRACT: Endoplasmic reticulum (ER)-associated degradation (ERAD) mediates the proteasomal clearance of proteins from the early secretory pathway. In this process, ubiquitinated substrates are extracted from membrane-embedded dislocation complexes by the AAA ATPase VCP and targeted to the cytosolic 26S proteasome. In addition to its well-established role in the degradation of misfolded proteins, ERAD also regulates the abundance of key proteins such as enzymes involved in cholesterol synthesis. However, due to the lack of generalizable methods, our understanding of the scope of proteins regulated targeted by ERAD remains limited. To overcome this obstacle, we developed a VCP-inhibitor substrate trapping approach (VISTA) to identify endogenous ERAD substrates. VISTA exploits the small-molecule VCP inhibitor CB5083 to trap ERAD substrates in a membrane-associated, ubiquitinated form.

INSTRUMENT(S): 6410 Triple Quadrupole LC/MS

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell

SUBMITTER: James Olzmann  

LAB HEAD: James Olzmann

PROVIDER: PXD008842 | Pride | 2018-03-12

REPOSITORIES: Pride