Down-regulation of nuclear protein ICBP90 by p53/p21Cip1/WAF1-dependent DNA-damage checkpoint signals contributes to cell cycle arrest at G1/S transition

Yoshimi Arima, Toru Hirota, Christian Bronner, Marc Mousli, Toshiyoshi Fujiwara, Shin Ichiro Niwa, Hiroyuki Ishikawa, Hideyuki Saya

研究成果: Article

109 引用 (Scopus)

抜粋

Checkpoints, which monitor DNA damage and regulate cell cycle progression, ensure genomic integrity and prevent the propagation of transformed cells. DNA damage activates the p53-dependent checkpoint pathway that induces expression of p21Cip1/WAF1, resulting in cell cycle arrest at G1/S transition by inhibition of cdk activity and DNA replication. ICBP90 was identified as a nuclear protein that binds to the TopoIIα gene promoter and is speculated to be involved in DNA replication. ICBP90 expression is cell cycle regulated in normal cells but stably high throughout cell cycle in various cancer cell lines. We here demonstrate that ICBP90 expression is down-regulated by the p53/p21Cip1/WAF1-dependent DNA damage checkpoint signals. The reduction of ICBP90 appeared to be caused by both transcriptional suppression and protein degradation. Adenoviral expression of p21Cip1/WAF1 directly led to ICBP90 reduction in p53-/- HCT116 cells without DNA damage. Furthermore, ICPB90 depletion by RNA interference significantly blocked G1/S transition after DNA damage in HeLa cells. The down-regulation of ICBP90 is an important mechanism for cell cycle arrest at G1/S transition, which is induced by the activation of a p53/p21Cip1/WAF1-dependent DNA-damage checkpoint. Deregulation of ICBP90 may impair the control of G1/S transition during checkpoint activation and lead to genomic instability.

元の言語English
ページ(範囲)131-142
ページ数12
ジャーナルGenes to Cells
9
発行部数2
DOI
出版物ステータスPublished - 2004 2 1
外部発表Yes

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

フィンガープリント Down-regulation of nuclear protein ICBP90 by p53/p21<sup>Cip1/WAF1</sup>-dependent DNA-damage checkpoint signals contributes to cell cycle arrest at G1/S transition' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

  • これを引用