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

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number37
JournalBMC Molecular Biology
Volume8
DOIs
Publication statusPublished - May 21 2007
Externally publishedYes

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Phosphorylation
Association reactions
Tumors
Cells
Transcriptional Activation
DNA
Transcription
Assays
Neoplasms
Genes
Chemical activation
Head and Neck Neoplasms
Immunoprecipitation
Messenger RNA
DNA Damage
Molecules
Transfection
Lung Neoplasms
Epithelial Cells
Breast Neoplasms

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

Cite this

Ishikawa, K., Ishii, H., Murakumo, Y., Mimori, K., Kobayashi, M., Yamamoto, K., ... Ichimura, K. (2007). Rad9 modulates the P21WAF1 pathway by direct association with p53. BMC Molecular Biology, 8, [37]. https://doi.org/10.1186/1471-2199-8-37

Rad9 modulates the P21WAF1 pathway by direct association with p53. / Ishikawa, Kazuhiro; Ishii, Hideshi; Murakumo, Yoshiki; Mimori, Koshi; Kobayashi, Masahiko; Yamamoto, Ken-ichi; Mori, Masaki; Nishino, Hiroshi; Furukawa, Yusuke; Ichimura, Keiichi.

In: BMC Molecular Biology, Vol. 8, 37, 21.05.2007.

Research output: Contribution to journalArticle

Ishikawa, K, Ishii, H, Murakumo, Y, Mimori, K, Kobayashi, M, Yamamoto, K, Mori, M, Nishino, H, Furukawa, Y & Ichimura, K 2007, 'Rad9 modulates the P21WAF1 pathway by direct association with p53', BMC Molecular Biology, vol. 8, 37. https://doi.org/10.1186/1471-2199-8-37
Ishikawa, Kazuhiro ; Ishii, Hideshi ; Murakumo, Yoshiki ; Mimori, Koshi ; Kobayashi, Masahiko ; Yamamoto, Ken-ichi ; Mori, Masaki ; Nishino, Hiroshi ; Furukawa, Yusuke ; Ichimura, Keiichi. / Rad9 modulates the P21WAF1 pathway by direct association with p53. In: BMC Molecular Biology. 2007 ; Vol. 8.
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