Caspase 3-specific cleavage of ubiquitin-specific peptidase 48 enhances drug-induced apoptosis in AML
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...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Cancer Biology & Therapy |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/15384047.2025.2459426 |
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| author | Zhanglin Zhang Xiang Lin Yaling Yang Xuemei Wang Yi Wang Xianbao Huang Miao Hong Wei Gao Hua He M. James You Yi Yang Guangyao Kong |
| author_facet | Zhanglin Zhang Xiang Lin Yaling Yang Xuemei Wang Yi Wang Xianbao Huang Miao Hong Wei Gao Hua He M. James You Yi Yang Guangyao Kong |
| author_sort | Zhanglin Zhang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-4e1e1f44937c4df295477720573f7345 |
| institution | Kabale University |
| issn | 1538-4047 1555-8576 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Cancer Biology & Therapy |
| spelling | doaj-art-4e1e1f44937c4df295477720573f73452025-01-29T11:43:41ZengTaylor & Francis GroupCancer Biology & Therapy1538-40471555-85762025-12-0126110.1080/15384047.2025.2459426Caspase 3-specific cleavage of ubiquitin-specific peptidase 48 enhances drug-induced apoptosis in AMLZhanglin Zhang0Xiang Lin1Yaling Yang2Xuemei Wang3Yi Wang4Xianbao Huang5Miao Hong6Wei Gao7Hua He8M. James You9Yi Yang10Guangyao Kong11National & 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, ChinaDepartments of Blood Transfusion, Institute of Transfusion, Jiangxi Key Laboratory of Transfusion, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, ChinaDepartment of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USADepartments of Blood Transfusion, Institute of Transfusion, Jiangxi Key Laboratory of Transfusion, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, ChinaDepartment of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USADepartment of Hematology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, ChinaDepartments of Blood Transfusion, Institute of Transfusion, Jiangxi Key Laboratory of Transfusion, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, ChinaDepartment of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USADepartment of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USADepartment of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USANational & 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, ChinaNational & 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, ChinaDysfunction 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.https://www.tandfonline.com/doi/10.1080/15384047.2025.2459426AMLapoptosisdeubiquitinationUSP48caspase 3 |
| spellingShingle | Zhanglin Zhang Xiang Lin Yaling Yang Xuemei Wang Yi Wang Xianbao Huang Miao Hong Wei Gao Hua He M. James You Yi Yang Guangyao Kong Caspase 3-specific cleavage of ubiquitin-specific peptidase 48 enhances drug-induced apoptosis in AML Cancer Biology & Therapy AML apoptosis deubiquitination USP48 caspase 3 |
| title | Caspase 3-specific cleavage of ubiquitin-specific peptidase 48 enhances drug-induced apoptosis in AML |
| title_full | Caspase 3-specific cleavage of ubiquitin-specific peptidase 48 enhances drug-induced apoptosis in AML |
| title_fullStr | Caspase 3-specific cleavage of ubiquitin-specific peptidase 48 enhances drug-induced apoptosis in AML |
| title_full_unstemmed | Caspase 3-specific cleavage of ubiquitin-specific peptidase 48 enhances drug-induced apoptosis in AML |
| title_short | Caspase 3-specific cleavage of ubiquitin-specific peptidase 48 enhances drug-induced apoptosis in AML |
| title_sort | caspase 3 specific cleavage of ubiquitin specific peptidase 48 enhances drug induced apoptosis in aml |
| topic | AML apoptosis deubiquitination USP48 caspase 3 |
| url | https://www.tandfonline.com/doi/10.1080/15384047.2025.2459426 |
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