Priority Research Papers:

TAp73 promotes cell survival upon genotoxic stress by inhibiting p53 activity

Dongshi Chen _, Lihua Ming, Fangdong Zou, Ye Peng, Bennett Van Houten, Jian Yu and Lin Zhang

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Oncotarget. 2014; 5:8107-8122. https://doi.org/10.18632/oncotarget.2440

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Dongshi Chen1,2, Lihua Ming1,3, Fangdong Zou1,2,4, Ye Peng1,2, Bennett Van Houten1,2, Jian Yu1,3, Lin Zhang1,2

1University of Pittsburgh Cancer Institute, Pittsburgh, PA, 15213, USA

2Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA

3Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA

4College of Life Sciences, Sichuan University, Chengdu, Sichuan, 610064, P.R. China

Correspondence to:

Dr. Lin Zhang, e-mail: [email protected]

Received: July 18, 2014     Accepted: July 18, 2014     Published: September 22, 2014


p53 plays a key role in regulating DNA damage response by suppressing cell cycle progression or inducing apoptosis depending on extent of DNA damage. However, it is not clear why mild genotoxic stress favors growth arrest, whereas excessive lesions signal cells to die. Here we showed that TAp73, a p53 homologue thought to have a similar function as p53, restrains the transcriptional activity of p53 and prevents excessive activation of its downstream targets upon low levels of DNA damage, which results in cell cycle arrest. Extensive DNA damage triggers TAp73 depletion through ubiquitin/proteasome-mediated degradation of E2F1, leading to enhanced transcriptional activation by p53 and subsequent induction of apoptosis. These findings provide novel insights into the regulation of p53 function and suggest that TAp73 keeps p53 activity in check in regulating cell fate decisions upon genotoxic stress.

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