2. Academic Validation
  3. Caspase 3-specific cleavage of ubiquitin-specific peptidase 48 enhances drug-induced apoptosis in AML

Caspase 3-specific cleavage of ubiquitin-specific peptidase 48 enhances drug-induced apoptosis in AML

  • Cancer Biol Ther. 2025 Dec;26(1):2459426. doi: 10.1080/15384047.2025.2459426.
Zhanglin Zhang 1 2,  Xiang Lin 2,  Yaling Yang 3,  Xuemei Wang 2,  Yi Wang 3,  Xianbao Huang 4,  Miao Hong 2,  Wei Gao 3,  Hua He 3,  M James You 3,  Yi Yang 1,  Guangyao Kong 1
Affiliations

Affiliations

  • 1 National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, Department of Hematology, Precision Medical Institute, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
  • 2 Departments of Blood Transfusion, Institute of Transfusion, Jiangxi Key Laboratory of Transfusion, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
  • 3 Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
  • 4 Department of Hematology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
PMID: 39878157 DOI: 10.1080/15384047.2025.2459426
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

AML; USP48; apoptosis; caspase 3; deubiquitination.

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