2013年10月
The RASSF6 Tumor Suppressor Protein Regulates Apoptosis and the Cell Cycle via MDM2 Protein and p53 Protein
JOURNAL OF BIOLOGICAL CHEMISTRY
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- 巻
- 288
- 号
- 42
- 開始ページ
- 30320
- 終了ページ
- 30329
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1074/jbc.M113.507384
- 出版者・発行元
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Ras association domain family (RASSF) 6 is a member of the C-terminal RASSF proteins such as RASSF1A and RASSF3. RASSF6 is involved in apoptosis in various cells under miscellaneous conditions, but it remains to be clarified how RASSF6 exerts tumor-suppressive roles. We reported previously that RASSF3 facilitates the degradation of MDM2, a major E3 ligase of p53, and stabilizes p53 to function as a tumor suppressor. In this study, we demonstrate that RASSF6 overexpression induces G(1)/S arrest in p53-positive cells. Its depletion prevents UV- and VP-16-induced apoptosis and G(1)/S arrest in HCT116 and U2OS cells. RASSF6-induced apoptosis partially depends on p53. RASSF6 binds MDM2 and facilitates its ubiquitination. RASSF6 depletion blocks the increase of p53 in response to UV exposure and up-regulation of p53 target genes. RASSF6 depletion delays DNA repair in UV- and VP-16-treated cells and increases polyploid cells after VP-16 treatment. These findings indicate that RASSF6 stabilizes p53, regulates apoptosis and the cell cycle, and functions as a tumor suppressor. Together with the previous reports regarding RASSF1A and RASSF3, the stabilization of p53 may be the common function of the C-terminal RASSF proteins.
- リンク情報
- ID情報
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- DOI : 10.1074/jbc.M113.507384
- ISSN : 0021-9258
- eISSN : 1083-351X
- PubMed ID : 24003224
- Web of Science ID : WOS:000329868100029