Che-1: A new effector of checkpoints signaling

Aristide Floridi, Maurizio Fanciulli

Research output: Contribution to journalArticle

Abstract

Che-1 is a RNA polymerase II binding protein involved in the transcriptional regulation of E2F target-genes and in cell proliferation. Recently, it has been shown that Che-1 accumulates in cells responding to genotoxic agents, such as Doxorubicin and ionizing radiations. The DNA damage-activated checkpoint kinases ATM and Chk2 interact with and phosphorylate Che-1, enhancing its accumulation and stability, and promoting Che-1-mediated transcription of p53-responsive genes and of p53 itself, as evidenced by microarray analysis. This transcriptional response is suppressed by expression of a Che-1 mutant lacking ATM and Chk2 phosphorylation amino acid residues, or by depletion of Che-1 by RNA silencing. In addition, chromatin immunoprecipitation analysis has shown that Che-1 is released from the E2F-target genes and recruited to the p21 and p53 promoters after DNA damage. Lastly, Che-1 contributes to the maintenance of the G2/M checkpoint in response to genotoxic stresses. These findings identify a new mechanism by which the checkpoint kinases regulate, via the novel effector Che-1, the p53 pathway.

Original languageEnglish
Pages (from-to)804-806
Number of pages3
JournalCell Cycle
Volume6
Issue number7
Publication statusPublished - Apr 1 2007

Keywords

  • AATF
  • ATM
  • Che-1
  • Chk2
  • DNA damage
  • G/M checkpoint
  • p53

ASJC Scopus subject areas

  • Cell Biology
  • Biochemistry
  • Molecular Biology

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