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mTOR inhibition acts as an unexpected checkpoint in p53-mediated tumor suppression.
Kon, Ning; Ou, Yang; Wang, Shang-Jui; Li, Huan; Rustgi, Anil K; Gu, Wei.
Afiliación
  • Kon N; Institute for Cancer Genetics, Department of Pathology and Cell Biology, Columbia University, New York, New York 10032, USA.
  • Ou Y; Institute for Cancer Genetics, Department of Pathology and Cell Biology, Columbia University, New York, New York 10032, USA.
  • Wang SJ; Institute for Cancer Genetics, Department of Pathology and Cell Biology, Columbia University, New York, New York 10032, USA.
  • Li H; Institute for Cancer Genetics, Department of Pathology and Cell Biology, Columbia University, New York, New York 10032, USA.
  • Rustgi AK; Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
  • Gu W; Institute for Cancer Genetics, Department of Pathology and Cell Biology, Columbia University, New York, New York 10032, USA.
Genes Dev ; 35(1-2): 59-64, 2021 01 01.
Article en En | MEDLINE | ID: mdl-33303641
Here, we showed that the acetylation-defective p53-4KR mice, lacking the ability of cell cycle arrest, senescence, apoptosis, and ferroptosis, were tumor prone but failed to develop early-onset tumors. By identifying a novel p53 acetylation site at lysine K136, we found that simultaneous mutations at all five acetylation sites (p53-5KR) diminished its remaining tumor suppression function. Moreover, the embryonic lethality caused by the deficiency of mdm2 was fully rescued in the background of p535KR/5KR , but not p534KR/4KR background. p53-4KR retained the ability to suppress mTOR function but this activity was abolished in p53-5KR cells. Notably, the early-onset tumor formation observed in p535KR/5KR and p53-null mice was suppressed upon the treatment of the mTOR inhibitor. These results suggest that p53-mediated mTOR regulation plays an important role in both embryonic development and tumor suppression, independent of cell cycle arrest, senescence, apoptosis, and ferroptosis.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Proteína p53 Supresora de Tumor / Serina-Treonina Quinasas TOR / Puntos de Control del Ciclo Celular / Neoplasias Límite: Animals Idioma: En Revista: Genes Dev Asunto de la revista: BIOLOGIA MOLECULAR Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Proteína p53 Supresora de Tumor / Serina-Treonina Quinasas TOR / Puntos de Control del Ciclo Celular / Neoplasias Límite: Animals Idioma: En Revista: Genes Dev Asunto de la revista: BIOLOGIA MOLECULAR Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos