| Literature DB >> 25701194 |
Jing-Hong Chen1, Peng Zhang, Wen-Dan Chen, Dan-Dan Li, Xiao-Qi Wu, Rong Deng, Lin Jiao, Xuan Li, Jiao Ji, Gong-Kan Feng, Yi-Xin Zeng, Jian-Wei Jiang, Xiao-Feng Zhu.
Abstract
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.Entities:
Keywords: AKT/PKB, v-akt murine thymoma viral oncogene homolog; AMPK, protein kinase, AMP-activated; ATG, autophagy-related; ATM; ATM, ATM serine/threonine kinase; Baf.A1, bafilomycin A1; CASP3, caspase 3, apoptosis-related cysteine peptidase; CCND1, cyclin D1; CDDP, cisplatin; CENPC/CENP-C, centromere protein C; CITED1/p300/CBP, Cbp/p300-interacting transactivator, with Glu/Asp-rich C-terminal domain, 1; CSNK2/CK2, casein kinase 2; DNA damage; DSBs, DNA double-strand breaks; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; GFP, green fluorescent protein; GLTSCR2/PICT-1, glioma tumor suppressor candidate region gene 2; GSK3B, glycogen synthase kinase 3 β; GST, glutathione S-transferase; H2A histone family; H2AFX; JUN; MAP1LC3/LC3, microtubule-associated protein 1 light chain 3; MTORC1, mechanistic target of rapamycin complex 1; MVP, major vault protein; NC, normal control; NEDD4, neural precursor cell expressed, developmentally down-regulated 4, E3 ubiquitin protein ligase; PAGE, polyacrylamide gel electrophoresis; PARP, poly (ADP-ribose) polymerase 1; PI3K, phosphoinositide 3-kinase; PMSF, phenylmethanesulfonyl fluoride; PPase, protein phosphatase; PTEN; PTEN, phosphatase and tensin homolog; PtdIns(3, 4, 5)P3, phosphatidylinositol (3, 4, 5)-trisphosphate; RAD51, RAD51 recombinase; RPS6KB/p70S6K; SDS, sodium dodecyl sulfate; SESN2, sestrin 2; SQSTM1/p62, sequestosome 1; TP53, tumor protein p53; TPT, topotecan; TUBA4A, tubulin, α, 4a; WT, wild type; YFP, yellow fluorescent protein; autophagy; jun proto-oncogene; member X; ribosomal protein S6 kinase, 70kDa; siRNA, small interfering RNA; topotecan
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Year: 2015 PMID： 25701194 PMCID： PMC4502816 DOI： 10.1080/15548627.2015.1009767
Source DB: PubMed Journal: Autophagy ISSN： 1554-8627 Impact factor: 16.016