Back to Search
Start Over
DNA Damage Triggers the Nuclear Accumulation of RASSF6 Tumor Suppressor Protein via CDK9 and BAF53 To Regulate p53 Target Gene Transcription.
- Source :
-
Molecular and cellular biology [Mol Cell Biol] 2022 Feb 17; Vol. 42 (2), pp. e0031021. Date of Electronic Publication: 2021 Dec 13. - Publication Year :
- 2022
-
Abstract
- RASSF6, a member of the tumor suppressor Ras-association domain family (RASSF) proteins, regulates cell cycle arrest and apoptosis via p53 and plays a tumor suppressor role. We previously reported that RASSF6 blocks MDM2-mediated p53 degradation and enhances p53 expression. In this study, we demonstrated that RASSF6 has nuclear localization and nuclear export signals and that DNA damage triggers the nuclear accumulation of RASSF6. We found that RASSF6 directly binds to BAF53, the component of SWI/SNF complex. DNA damage induces CDK9-mediated phosphorylation of BAF53, which enhances the interaction with RASSF6 and increases the amount of RASSF6 in the nucleus. Subsequently, RASSF6 augments the interaction between BAF53 and BAF60a, another component of the SWI/SNF complex, and further promotes the interaction of BAF53 and BAF60a with p53. BAF53 silencing or BAF60a silencing attenuates RASSF6-mediated p53 target gene transcription and apoptosis. Thus, RASSF6 is involved in the regulation of DNA damage-induced complex formation, including BAF53, BAF60a, and p53.
- Subjects :
- Actins genetics
Apoptosis physiology
Apoptosis Regulatory Proteins genetics
Cell Cycle Checkpoints genetics
Cell Cycle Checkpoints physiology
Chromosomal Proteins, Non-Histone genetics
Cyclin-Dependent Kinase 9 genetics
DNA Damage physiology
DNA-Binding Proteins genetics
Humans
Monomeric GTP-Binding Proteins genetics
Tumor Suppressor Proteins metabolism
Actins metabolism
Apoptosis Regulatory Proteins metabolism
Chromosomal Proteins, Non-Histone metabolism
Cyclin-Dependent Kinase 9 metabolism
DNA Damage genetics
DNA-Binding Proteins metabolism
Transcription, Genetic genetics
Tumor Suppressor Protein p53 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5549
- Volume :
- 42
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Molecular and cellular biology
- Publication Type :
- Academic Journal
- Accession number :
- 34898277
- Full Text :
- https://doi.org/10.1128/MCB.00310-21