2022年2月17日
DNA damage triggers the nuclear accumulation of RASSF6 tumor suppressor protein via CDK9 and BAF53 to regulate p53-target gene transcription
Molecular and Cellular Biology
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- 巻
- 42
- 号
- 2
- 開始ページ
- e0031021
- 終了ページ
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1128/mcb.00310-21
- 出版者・発行元
- American Society for Microbiology
RASSF6, a member of the tumor suppressor Ras-association domain family (RASSF) proteins, regulates cell cycle arrest and apoptosis
<italic>via</italic>
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 SWI/SNF complex, and further promotes the interaction of BAF53 and BAF60a with p53.
<italic>BAF53</italic>
silencing or
<italic>BAF60a</italic>
silencing attenuates RASSF6-mediated p53-target gene transcription and apoptosis. Thus, RASSF6 is involved in the regulation of DNA damage-induced complex formation including CDK9, BAF53, BAF60a, and p53.
<italic>via</italic>
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 SWI/SNF complex, and further promotes the interaction of BAF53 and BAF60a with p53.
<italic>BAF53</italic>
silencing or
<italic>BAF60a</italic>
silencing attenuates RASSF6-mediated p53-target gene transcription and apoptosis. Thus, RASSF6 is involved in the regulation of DNA damage-induced complex formation including CDK9, BAF53, BAF60a, and p53.
- リンク情報
- ID情報
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- DOI : 10.1128/mcb.00310-21
- ISSN : 0270-7306
- eISSN : 1098-5549