| Autor: |
Qincai Dong, Dapei Li, Huailong Zhao, Xun Zhang, Yue Liu, Yong Hu, Yi Yao, Lin Zhu, Guang-Fei Wang, Hainan Liu, Ting Gao, Xiayang Niu, Tong Zheng, Caiwei Song, Di Wang, Yu Bai, Jing Jin, Zijing Liu, Yanwen Jin, Ping Li, Cheng Cao, Xuan Liu |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Cell Death and Disease, Vol 13, Iss 4, Pp 1-14 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2041-4889 |
| DOI: |
10.1038/s41419-022-04748-2 |
| Popis: |
Abstract The anti-apoptotic protein HAX-1 has been proposed to modulate mitochondrial membrane potential, calcium signaling and actin remodeling. HAX-1 mutation or deficiency results in severe congenital neutropenia (SCN), loss of lymphocytes and neurological impairments by largely unknown mechanisms. Here, we demonstrate that the activation of c-Abl kinase in response to oxidative or genotoxic stress is dependent on HAX-1 association. Cellular reactive oxygen species (ROS) accumulation is inhibited by HAX-1-dependent c-Abl activation, which greatly contributes to the antiapoptotic role of HAX-1 in stress. HAX-1 (Q190X), a loss-of-function mutant responsible for SCN, fails to bind with and activate c-Abl, leading to dysregulated cellular ROS levels, damaged mitochondrial membrane potential and eventually apoptosis. The extensive apoptosis of lymphocytes and neurons in Hax-1-deficient mice could also be remarkably suppressed by c-Abl activation. These findings underline the important roles of ROS clearance in HAX-1-mediated anti-apoptosis by c-Abl kinase activation, providing new insight into the pathology and treatment of HAX-1-related hereditary disease or tumorigenesis. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
Full text from SpringerLink