
Faculty, Staff and Student Publications
Publication Date
12-1-2025
Journal
Cancer Biology & Therapy
Abstract
Dysfunction or dysregulation of deubiquitination is closely related to the initiation and development of multiple cancers. Targeted regulation of deubiquitination has been recognized as an important strategy in tumor therapy. However, the mechanism by which drugs regulate deubiquitinase is not clear. Here, we identified ubiquitin-specific peptidase 48 (USP48), a member of the ubiquitin-specific protease family highly expressed in various tumors, as a specific substrate for the activated caspase-3. During drug induced apoptosis of AML cells, activated caspase-3 cleaves USP48 through recognizing the conservative motif DEQD located at 611-614 sites of human USP48. Subsequent analysis showed that the cleavage USP48 N-terminal fragment which contains catalytic active domain is easily degraded by ubiquitination. Meanwhile knockdown experiment showed that inhibiting the expression of USP48 could also promotes apoptosis and enhance the efficacy of chemotherapy drugs. Altogether, these results suggest that targeting USP48 may represent a novel therapeutic strategy in AML.
Keywords
Humans, Apoptosis, Leukemia, Myeloid, Acute, Caspase 3, Cell Line, Tumor, Ubiquitin-Specific Proteases, Antineoplastic Agents, Ubiquitination, AML, USP48, apoptosis, caspase 3, deubiquitination
DOI
10.1080/15384047.2025.2459426
PMID
39878157
PMCID
PMC11781246
PubMedCentral® Posted Date
1-29-2025
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Medical Genetics Commons, Oncology Commons