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

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

Received 7 May 2019

Accepted for publication 14 August 2019

Published 23 September 2019 Volume 2019:11 Pages 8619—8633

DOI https://doi.org/10.2147/CMAR.S214826

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Dr Antonella D'Anneo


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 work

Correspondence: Yonghong Lei
Department of Plastic Surgery, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100853, People’s Republic of China
Tel +86 10 13161281016
Email lyhhlx@126.com
Yi Hu
Department of Oncology, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100853, People’s Republic of China
Tel +86 10 13911031186
Email huyi0401@aliyun.com

Background: 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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