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Ataxia-Telangiectasia Mutated Is Involved in Autolysosome Formation.
Hwang, Mihwa; Jun, Dong Wha; Song, Bo Ram; Shim, Hanna; Lee, Chang-Hun; Kim, Sunshin.
Afiliación
  • Hwang M; Research Institute, National Cancer Center, Goyang 10408, Republic of Korea.
  • Jun DW; Research Institute, National Cancer Center, Goyang 10408, Republic of Korea.
  • Song BR; Research Institute, National Cancer Center, Goyang 10408, Republic of Korea.
  • Shim H; Research Institute, National Cancer Center, Goyang 10408, Republic of Korea.
  • Lee CH; Research Institute, National Cancer Center, Goyang 10408, Republic of Korea.
  • Kim S; Research Institute, National Cancer Center, Goyang 10408, Republic of Korea.
Biomol Ther (Seoul) ; 31(5): 559-565, 2023 Sep 01.
Article en En | MEDLINE | ID: mdl-36941082
ABSTRACT
Ataxia-telangiectasia mutated (ATM), a master kinase of the DNA damage response (DDR), phosphorylates a multitude of substrates to activate signaling pathways after DNA double-strand breaks (DSBs). ATM inhibitors have been evaluated as anticancer drugs to potentiate the cytotoxicity of DNA damage-based cancer therapy. ATM is also involved in autophagy, a conserved cellular process that maintains homeostasis by degrading unnecessary proteins and dysfunctional organelles. In this study, we report that ATM inhibitors (KU-55933 and KU-60019) provoked accumulation of autophagosomes and p62 and restrained autolysosome formation. Under autophagy-inducing conditions, the ATM inhibitors caused excessive autophagosome accumulation and cell death. This new function of ATM in autophagy was also observed in numerous cell lines. Repression of ATM expression using an siRNA inhibited autophagic flux at the autolysosome formation step and induced cell death under autophagy-inducing conditions. Taken together, our results suggest that ATM is involved in autolysosome formation and that the use of ATM inhibitors in cancer therapy may be expanded.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Biomol Ther (Seoul) Año: 2023 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Biomol Ther (Seoul) Año: 2023 Tipo del documento: Article
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