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bioRxiv · 10.1101/2020.05.14.096982

p53 induces ARTS to promote mitochondrial apoptosis

Hao, Q.·Chen, J.·Liao, J.·Huang, Y.·Larisch, S.·Zeng, S. X.·Lu, H.·Zhou, X.
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Abstract

Apoptosis Related protein in TGF-{beta} Signaling pathway (ARTS) was originally discovered in cells undergoing apoptosis in response to TGF-{beta}, but ARTS also acts downstream of many other apoptotic stimuli. ARTS induces apoptosis by antagonizing the anti-apoptotic proteins XIAP and Bcl-2. Here, we identified the pro-apoptotic Sept4/ARTS gene as a p53-responsive target gene. Ectopic p53 and a variety of p53-inducing agents increased both mRNA and protein levels of ARTS, whereas ablation of p53 reduced ARTS expression in response to multiple stress conditions. Also, {gamma}-irradiation induced p53-dependent ARTS expression in mice. Consistently, p53 binds to the responsive DNA element on the ARTS promoter and transcriptionally activated the promoter-driven expression of a luciferase reporter gene. Interestingly, ARTS binds to and sequesters p53 at mitochondria, enhancing the interaction of the latter with Bcl-XL. Ectopic ARTS markedly augments DNA damage stress- or Nutlin-3-triggered apoptosis, while ablation of ARTS preferentially impairs p53-induced apoptosis. Altogether, these findings demonstrate that ARTS collaborates with p53 in mitochondria-engaged apoptosis.

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Hao, Q., Chen, J., Liao, J., Huang, Y., Larisch, S., Zeng, S. X., Lu, H., Zhou, X.. 2020-05-16. p53 induces ARTS to promote mitochondrial apoptosis. https://doi.org/10.1101/2020.05.14.096982

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