Rad9 modulates the P21WAF1 pathway by direct association with p53

フォーマット:

論文

責任表示:

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

言語:

英語

出版情報:

BioMed Central, 2007-04-21

著者名:

Ishikawa, Kazuhiro

Ishii, Hideshi

Murakumo, Yoshiki

Mimori, Koshi

Kobayashi, Masahiko

Yamamoto, Ken-ichi

Mori, Masaki

Nishino, Hiroshi

Furukawa, Yusuke

Ichimura, Keiichi

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掲載情報:

BMC Molecular Biology

ISSN:

1471-2199      

巻:

8

バージョン:

author

概要:

金沢大学がん研究所がん分子細胞制御<br />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. 続きを見る

URL:

http://hdl.handle.net/2297/6945