c-MYC-USP49-BAG2 axis promotes proliferation and chemoresistance of colorectal cancer cells in vitro.
Biochem Biophys Res Commun
; 607: 117-123, 2022 06 04.
Article
in En
| MEDLINE
| ID: mdl-35367823
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colorectal Neoplasms
/
Proto-Oncogene Proteins c-myc
/
Molecular Chaperones
/
Ubiquitin Thiolesterase
Limits:
Humans
Language:
En
Journal:
Biochem Biophys Res Commun
Year:
2022
Document type:
Article