Title

c-MYC-USP49-BAG2 axis promotes proliferation and chemoresistance of colorectal cancer cells in vitro.

Document Type

Article

Publication Date

6-4-2022

Publication Title

Biochemical and biophysical research communications

Keywords

JGM, Carcinogenesis, Cell Line, Tumor, Cell Proliferation, Colorectal Neoplasms, Drug Resistance, Neoplasm, Humans, Molecular Chaperones, Proto-Oncogene Proteins c-myc, Ubiquitin Thiolesterase

JAX Source

Biochem Biophys Res Comm 2022 Jun 4; 607:117-123

Volume

607

First Page

117

Last Page

123

ISSN

1090-2104

PMID

35367823

DOI

https://doi.org/10.1016/j.bbrc.2022.03.138

Abstract

Deubiquitinases (DUBs) play critical roles in tumorigenesis and are emerging as potential therapeutic targets. However, it remains less clear which DUBs may play important roles and represent a realistic vulnerability for a particular type of tumor. Here we revealed that Ubiquitin Specific Peptidase 49 (USP49) is transcriptionally activated by c-MYC in colorectal cancer (CRC), and CRC patients with elevated USP49 levels exhibited significantly shorter survival. Knockdown of USP49 markedly inhibited CRC cell proliferation, colony formation, and chemotherapy resistance in vitro. Investigation of mechanisms unravels that USP49 deubiquitinates and stabilizes Bcl-2-Associated Athanogene 2 (BAG2), a well-known protein that antagonizes apoptosis and enables adaptive response of CRC cells. This study identified a novel mechanism by which USP49 promotes CRC cell survival by stabilizing BAG2 through the c-MYC-USP49-BAG2 axis, indicating that USP49 may become a potential therapeutic target for CRC.

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