p53 induces ARTS to promote mitochondrial apoptosis
| Autor: | Hua Lu, Sarit Larisch, Shelya X. Zeng, Jun-Ming Liao, Yu Gan, Jiaxiang Chen, Qian Hao, Yingdan Huang, Xiang Zhou |
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| Rok vydání: | 2021 |
| Předmět: |
Transcriptional Activation
Cancer Research Indoles DNA damage Immunology bcl-X Protein Antineoplastic Agents Apoptosis Mitochondrion Article Stress signalling Cellular and Molecular Neuroscience Phenothiazines Neoplasms Animals Humans lcsh:QH573-671 Promoter Regions Genetic Tumour-suppressor proteins Gene Mice Knockout Messenger RNA Binding Sites lcsh:Cytology Chemistry Cell Biology HCT116 Cells Mitochondria Up-Regulation XIAP Cell biology Gene Expression Regulation Neoplastic Tumor Suppressor Protein p53 Signal transduction Septins Protein Binding Signal Transduction Transforming growth factor |
| Zdroj: | Cell Death & Disease Cell Death and Disease, Vol 12, Iss 2, Pp 1-11 (2021) |
| ISSN: | 2041-4889 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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