Rad9 modulates the P21WAF1 pathway by direct association with p53 Rad9 modulates the P21WAF1 pathway by direct association with p53

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Abstract

金沢大学がん研究所がん分子細胞制御

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.

Journal

  • BMC Molecular Biology

    BMC Molecular Biology (8), 37, 2007-04-21

    BioMed Central

Cited by:  1

Codes

  • NII Article ID (NAID)
    120001138323
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    1471-2199
  • Data Source
    CJPref  IR 
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