Proteomics

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Temporal proteomics of p97/VCP inhibition

ABSTRACT: To facilitate the development of p97 inhibitors as potential therapeutic agents and help define their clinical application, it is necessary to dissect the mechanism of action (MOA) of p97 inhibitors and compare them with proteasome inhibitors. Moreover, identifying specific cellular markers is critical for both the drug discovery and development process, to help validate candidate drugs and quantify their effect. In this study, we performed proteomic analysis and systematically compared p97 shRNA knockdown (KD), and three p97 inhibitors, with the proteasome inhibitor MG132 in HCT116 colon cancer cells. Through proteomic analyses we uncover the specific molecular mechanism by which p97 inhibition is distinct from proteasome inhibition, potentially relevant to understanding the efficacious effects of the former in solid tumors.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

DISEASE(S): Colon Cancer

SUBMITTER: Shan Li  

LAB HEAD: Shan Li

PROVIDER: PXD025094 | Pride | 2021-12-15

REPOSITORIES: pride

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HCT116_FAIMS_no_FAIMS_RSTMS3_TMTpro.mzML Mzml
HCT116_FAIMS_no_FAIMS_RSTMS3_TMTpro.mzid.gz Mzid
HCT1_TMTpro_03July20_03.raw Raw
HCT1_TMTpro_09July20_FAIMS_60vMS3.raw Raw
HCT2_TMTpro_03July20_03.raw Raw
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Publications

Temporal proteomics reveal specific cell cycle oncoprotein downregulation by p97/VCP inhibition.

Wang Feng F   Li Shan S   Houerbi Nadia N   Chou Tsui-Fen TF  

Cell chemical biology 20211129 3

Targeting protein quality control (PQC) pathways using proteasome or p97/VCP inhibition can effectively treat blood tumors. However, in solid tumors, only p97/VCP inhibitors are effective. To probe this difference in efficacy, we tracked HCT116 colon cancer cells using temporal proteomics to define the cellular and molecular responses to proteasome and p97 inhibition. Proteins involved in general PQC pathways were similarly upregulated by both treatments, suggesting that the proteotoxic stress c  ...[more]

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