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p53 induces ARTS to promote mitochondrial apoptosis
- Source :
- Cell Death & Disease, Cell Death and Disease, Vol 12, Iss 2, Pp 1-11 (2021)
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 20414889
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Cell Death & Disease
- Accession number :
- edsair.doi.dedup.....8e183c8781b860b6dd40577819fc58e2