Proteomics

Dataset Information

0

Proteomic profiling of VCP substrates links VCP to K6-linked ubiquitylation and c-Myc function


ABSTRACT: VCP is an evolutionary conserved ubiquitin-dependent ATPase that mediates the degradation of proteins through the ubiquitin-proteasome pathway. Despite the central role of VCP in the regulation of protein homeostasis, identity and nature of its cellular substrates remain poorly defined. Here, we combined chemical inhibition of VCP and quantitative ubiquitin remnant profiling to assess the effect of VCP inhibition on the ubiquitin-modified proteome and to probe the substrate spectrum of VCP in human cells. We demonstrate that inhibition of VCP perturbs cellular ubiquitylation and increases ubiquitylation of a different subset of proteins compared to proteasome inhibition. VCP inhibition globally upregulates K6-linked ubiquitylation that is dependent on the HECT-type ubiquitin E3 ligase HUWE1. We report ~450 putative VCP substrates, many of which function in nuclear processes, including gene expression, DNA repair and cell cycle. Moreover, we identify that VCP regulates the level and activity of the transcription factor c-Myc.

OTHER RELATED OMICS DATASETS IN: PRJNA419745

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Petra Beli  

LAB HEAD: Petra Beli

PROVIDER: PXD003936 | Pride | 2018-02-09

REPOSITORIES: Pride

altmetric image

Publications

Proteomic profiling of VCP substrates links VCP to K6-linked ubiquitylation and c-Myc function.

Heidelberger Jan B JB   Voigt Andrea A   Borisova Marina E ME   Petrosino Giuseppe G   Ruf Stefanie S   Wagner Sebastian A SA   Beli Petra P  

EMBO reports 20180221 4


Valosin-containing protein (VCP) is an evolutionarily conserved ubiquitin-dependent ATPase that mediates the degradation of proteins through the ubiquitin-proteasome pathway. Despite the central role of VCP in the regulation of protein homeostasis, identity and nature of its cellular substrates remain poorly defined. Here, we combined chemical inhibition of VCP and quantitative ubiquitin remnant profiling to assess the effect of VCP inhibition on the ubiquitin-modified proteome and to probe the  ...[more]

Similar Datasets

2018-02-08 | GSE107313 | GEO
2006-08-23 | E-MEXP-817 | biostudies-arrayexpress
2019-08-19 | PXD011772 | Pride
2022-06-23 | PXD032903 | Pride
2021-05-03 | PXD020909 | Pride
| PRJNA419745 | ENA
2016-06-09 | PXD003627 | Pride
2023-01-01 | GSE162068 | GEO
2023-11-15 | PXD042937 | Pride
2023-01-01 | GSE162483 | GEO