| Autor: |
Shuzhang Sun, Yixuan Cheng, Wanxin Hou, Yinjie Yan, Tian Meng, Hegen Li, Ning Xiao |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Biochemistry and Biophysics Reports, Vol 37, Iss , Pp 101650- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2405-5808 |
| DOI: |
10.1016/j.bbrep.2024.101650 |
| Popis: |
Chemotherapy is the most common treatment for acute lymphoblastic leukemia (ALL). However, many ALL patients eventually develop relapse and treating relapsed ALL has always been challenging. Therefore, exploring the resistance mechanism of chemotherapeutic drugs and proposing feasible intervention strategies are of great significance for ALL treatment. Here, we show that SENP8, whose coding protein is an important deNEDDylase targeting the substrate for deNEDDylation, is highly expressed in relapsed ALL specimens. Interestingly, overexpressing SENP8 specifically reduces the chemosensitivity of ALL cells to etoposide (VP-16) and significantly alleviates the proapoptotic effect of VP-16 on ALL cells. By contrast, NEDDylation inhibition reduces the chemosensitivity of ALL cells to VP-16. Furthermore, VP-16 induces SENP8 accumulation and the instability of MDM2 as well as the stabilization of p53 in ALL cells, and SENP8 knockdown can sensitize ALL cells to VP-16. Our study reveals a novel function of SENP8 in ALL and that VP-16-induced SENP8 confers a feed-back drug resistance on ALL cells, suggesting a possibility of overcoming the chemotherapeutic resistance to VP-16 via targeting SENP8. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
