Loss of p53-regulatory protein IFI16 induces NBS1 leading to activation of p53-mediated checkpint by phosphorylation of p53 SER37

Hideyuki Tawara, Nobuko Fujiuchi, Juan Sironi, Sarah Martin, Jason Aglipay, Mutsuko Ouchi, Makoto Taga, Phang Lang Chen, Toru Ouchi

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Our previous results that IFI16 is involved in p53 transcription activity under conditions of ionizing radiation (IR), and that the protein is frequently lost in human breast cancer cell lines and breast adenocarcinoma tissues suggesting that IFI16 plays a crucial role in controlling cell growth. Here, we show that loss of IFI16 by RNA interference in cell culture causes elevated phosphorylation of p53 Ser37 and accumulated NBS1 (nibrin) and p21WAF1, leading to growth retardation. Consistent with these observations, doxycyclin-induced NBS1 caused accumulation of p21WAF1 and increased phosphorylation of p53 Ser37, leading to cell cycle arrest in G1 phase. Wortmannin treatment was found to decrease p53 Ser37 phosphorylation in NBS-induced cells. These results suggest that loss of IFI16 activates p53 checkpoint through NBS1-DNA-PKcs pathway.

Original languageEnglish (US)
Pages (from-to)240-248
Number of pages9
JournalFrontiers in Bioscience
Volume13
Issue number1
DOIs
StatePublished - May 2 2008

Keywords

  • Cell cycle checkpoint
  • DNA damage
  • Review
  • p53

ASJC Scopus subject areas

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

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    Tawara, H., Fujiuchi, N., Sironi, J., Martin, S., Aglipay, J., Ouchi, M., Taga, M., Chen, P. L., & Ouchi, T. (2008). Loss of p53-regulatory protein IFI16 induces NBS1 leading to activation of p53-mediated checkpint by phosphorylation of p53 SER37. Frontiers in Bioscience, 13(1), 240-248. https://doi.org/10.2741/2674