p53 induces ARTS to promote mitochondrial apoptosis

Qian Hao, Jiaxiang Chen, Junming Liao, Yingdan Huang, Yu Gan, Sarit Larisch, Shelya X. Zeng, Hua Lu, Xiang Zhou

Research output: Contribution to journalArticlepeer-review

Abstract

Apoptosis related protein in TGF-β signaling pathway (ARTS) was originally discovered in cells undergoing apoptosis in response to TGF-β, 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, γ-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.

Original languageEnglish
Article number204
JournalCell Death and Disease
Volume12
Issue number2
DOIs
StatePublished - Feb 2021

Bibliographical note

Funding Information:
The study was supported in part by the National Natural Science Foundation of China (Nos. 81874053, 82072879, and 81702352) to X.Z. and Q.H.; Reynolds and Ryan Families Chair Fund of Translational Cancer to H.L.; and Israel Science Foundation (ISF) Grant 822/12 to S.L.

Publisher Copyright:
© 2021, The Author(s).

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

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