Cancer Management and Research (Sep 2019)

A New Regulatory Mechanism Between P53 And YAP Crosstalk By SIRT1 Mediated Deacetylation To Regulate Cell Cycle And Apoptosis In A549 Cell Lines

  • Yuan F,
  • Wang J,
  • Li R,
  • Zhao X,
  • Zhang Y,
  • Liu B,
  • Lei Y,
  • Hu Y

Journal volume & issue
Vol. Volume 11
pp. 8619 – 8633

Abstract

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Fang Yuan,1,* Jinliang Wang,1,* Ruixin Li,1,* Xiao Zhao,1 Yuxuan Zhang,2 Biao Liu,3 Yonghong Lei,4 Yi Hu1 1Department of Oncology, Chinese PLA General Hospital, Beijing 100853, People’s Republic of China; 2Princeton International School of Mathematics and Science, Princeton, NJ 08540, USA; 3Department of Biological Analysis, Explore (Beijing) Biotech Co, Ltd, Beijing 100091, People’s Republic of China; 4Department of Plastic Surgery, Chinese PLA General Hospital, Beijing 100853, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yonghong LeiDepartment of Plastic Surgery, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100853, People’s Republic of ChinaTel +86 10 13161281016Email [email protected] HuDepartment of Oncology, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100853, People’s Republic of ChinaTel +86 10 13911031186Email [email protected]: Yes-associated protein (YAP) is downstream of the Hippo signaling pathway, which regulates several cellular processes. P53 is a key transcriptional regulator that responds to a variety of cellular stresses and regulates key cellular processes such as DNA repair, cell-cycle progression, angiogenesis, and apoptosis. Overexpression of YAP antagonizes P53 activity and targets its expression. However, the mechanism that underlies the post-transcriptional crosstalk between P53 and YAP has not been well dissected.Methods: We performed an integrated analysis and found that SIRT1 is a key candidate that connects YAP and P53 by modulating their acetylation.Results: We found that YAP promotes P53 deacetylation, promotes cell survival by inhibiting P53-induced G0/G1 arrest and apoptosis in A549 cells. Conversely, P53 enhances YAP acetylation, and decreases A549 cell survival by strengthening YAP acetylation-induced G0/G1 arrest and apoptosis both in vitro and in vivo.Conclusion: Our results demonstrate that SIRT1 is responsible for YAP and P53 deacetylation of specific residues, and reveal for the first time, a new regulatory mechanism of P53 and YAP crosstalk by SIRT1-mediated deacetylation, which may be involved in lung tumorigenesis.Keywords: P53, YAP, SIRT1, crosstalk

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