期刊
AUTOPHAGY
卷 11, 期 2, 页码 239-252出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2015.1009767
关键词
ATM; autophagy; DNA damage; PTEN; topotecan
类别
资金
- National Basic Research Program of China [2012CB967004, 2011CB504300]
- National Natural Science Foundation of China [81272199, 81272895]
- Natural Science Foundation of Guangdong [S2011020002759]
PTEN (phosphatase and tensin homolog), a tumor suppressor frequently mutated in human cancer, has various cytoplasmic and nuclear functions. PTEN translocates to the nucleus from the cytoplasm in response to oxidative stress. However, the mechanism and function of the translocation are not completely understood. In this study, topotecan (TPT), a topoisomerase I inhibitor, and cisplatin (CDDP) were employed to induce DNA damage. The results indicate that TPT or CDDP activates ATM (ATM serine/threonine kinase), which phosphorylates PTEN at serine 113 and further regulates PTEN nuclear translocation in A549 and HeLa cells. After nuclear translocation, PTEN induces autophagy, in association with the activation of the p-JUN-SESN2/AMPK pathway, in response to TPT. These results identify PTEN phosphorylation by ATM as essential for PTEN nuclear translocation and the subsequent induction of autophagy in response to DNA damage.
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