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

ABSTRACT: 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 caused by inhibitors does not explain the differential therapeutic effectiveness. Unexpectedly, proteins specifically dysregulated by two p97 inhibitors are involved in cell cycle control. Indeed, eleven cell cycle proteins were downregulated by p97 inhibition but not by proteasome inhibition. Wester

SUBMITTER: Wang F 

PROVIDER: S-EPMC8934257 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature