Rad9 modulates the P21WAF1 pathway by direct association with p53

Kazuhiro Ishikawa, Hideshi Ishii, Yoshiki Murakumo, Koshi Mimori, Masahiko Kobayashi, Ken Ichi Yamamoto, Masaki Mori, Hiroshi Nishino, Yusuke Furukawa, Keiichi Ichimura

研究成果: Contribution to journalArticle査読

14 被引用数 (Scopus)

抄録

Background: Previous studies suggest that human RAD9 (hRad9), encoding a DNA damage checkpoint molecule, which is frequently amplified in epithelial tumor cells of breast, lung, head and neck cancer, participates in regulation of the tumor suppressor p53-dependent transactivation of pro-survival P21WAF1. This study examined the exact mechanism of the hRad9 function, especially through the phosphorylation of the C-terminus, in the transcription regulation of P21WAF1. Results: The transfection of phosphorylation-defective hRAD9 mutants of C-terminus resulted in reduction of the p53-dependent P21WAF1 transactivation; the knockdown of total hRad9 elicited an increased P21WAF1 mRNA expression. Immunoprecipitation and a ChIP assay showed that hRad9 and p53 formed a complex and both were associated with two p53-consensus DNA-binding sequences in the 5′ region of P21WAF1 gene. The association was reduced in the experiment of phosphorylation-defective hRAD9 mutants. Conclusion: The present study indicates the direct involvement of hRad9 in the p53-dependent P21WAF1 transcriptional mechanism, presumably via the phosphorylation sites, and alterations of the hRad9 pathway might therefore contribute to the perturbation of checkpoint activation in cancer cells.

本文言語英語
論文番号37
ジャーナルBMC Molecular Biology
8
DOI
出版ステータス出版済み - 5 21 2007

All Science Journal Classification (ASJC) codes

  • Molecular Biology

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