期刊
AGING-US
卷 14, 期 15, 页码 6128-6148出版社
IMPACT JOURNALS LLC
关键词
apoptosis; alpha B-crystallin; lens; cataract
资金
- National Natural Science Foundation of China [81770910, 8216067]
- Basic Research Project from the Guizhou Provincial Science and Technology Projects [ZK[2021]-427]
Research has shown that Mab21L1 promotes survival of lens epithelial cells by regulating the expression of αB-crystallin and suppressing the ATR/CHK1/p53 pathway. This finding contributes to a better understanding of the functional mechanism of Mab21L1.
The male abnormal gene family 21 (mab21), was initially identified in C. elegans. Since its identification, studies from different groups have shown that it regulates development of ocular tissues, brain, heart and liver. However, its functional mechanism remains largely unknown. Here, we demonstrate that Mab21L1 promotes survival of lens epithelial cells. Mechanistically, Mab21L1 upregulates expression of alpha B-crystallin. Moreover, our results show that alpha B-crystallin prevents stress-induced phosphorylation of p53 at S-20 and S-37 through abrogating the activation of the upstream kinases, ATR and CHK1. As a result of suppressing p53 activity by alpha B-crystallin, Mab21L1 downregulates expression of Bak but upregulates Mcl-1 during stress insult. Taken together, our results demonstrate that Mab21L1 promotes survival of lens epithelial cells through upregulation of alpha B-crystallin to suppress ATR/CHK1/p53 pathway.
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