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- Title
Inhibition of USP2 Enhances TRAIL-Mediated Cancer Cell Death through Downregulation of Survivin.
- Authors
Lee, Tak Gyeom; Woo, Seon Min; Seo, Seung Un; Kim, Shin; Park, Jong-Wook; Chang, Young-Chae; Kwon, Taeg Kyu
- Abstract
Ubiquitin-specific protease 2 (USP2) is a deubiquitinase belonging to the USPs subfamily. USP2 has been known to display various biological effects including tumorigenesis and inflammation. Therefore, we aimed to examine the sensitization effect of USP2 in TRAIL-mediated apoptosis. The pharmacological inhibitor (ML364) and siRNA targeting USP2 enhanced TNF-related apoptosis-inducing ligand (TRAIL)-induced cancer cell death, but not normal cells. Mechanistically, USP2 interacted with survivin, and ML364 degraded survivin protein expression by increasing the ubiquitination of survivin. Overexpression of survivin or USP2 significantly prevented apoptosis through cotreatment with ML364 and TRAIL, whereas a knockdown of USP2 increased sensitivity to TRAIL. Taken together, our data suggested that ML364 ubiquitylates and degrades survivin, thereby increasing the reactivity to TRAIL-mediated apoptosis in cancer cells.
- Subjects
CELL death; SURVIVIN (Protein); CANCER cells; TRAIL protein; DEUBIQUITINATING enzymes
- Publication
International Journal of Molecular Sciences, 2023, Vol 24, Issue 16, p12816
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms241612816