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.
Recommended Citation
Tu R,
Kang W,
Kang Y,
Chen Z,
Zhang P,
Xiong X,
Ma J,
Du R,
Zhang C.
c-MYC-USP49-BAG2 axis promotes proliferation and chemoresistance of colorectal cancer cells in vitro. Biochem Biophys Res Comm 2022 Jun 4; 607:117-123