Che-1 phosphorylation by ATM/ATR and Chk2 kinases activates p53 transcription and the G2/M checkpoint

Tiziana Bruno, Francesca De Nicola, Simona Iezzi, Daniele Lecis, Carmen D'Angelo, Monica Di Padova, Nicoletta Corbi, Leopoldo Dimiziani, Laura Zannini, Christian Jekimovs, Marco Scarsella, Alessandro Porrello, Alberto Chersi, Marco Crescenzi, Carlo Leonetti, Kum Kum Khanna, Silvia Soddu, Aristide Floridi, Claudio Passananti, Domenico DeliaMaurizio Fanciulli

Research output: Contribution to journalArticlepeer-review

Abstract

Che-1 is a RNA polymerase II-binding protein involved in the transcription of E2F target genes and induction of cell proliferation. Here we show that Che-1 contributes to DNA damage response and that its depletion sensitizes cells to anticancer agents. The checkpoint kinases ATM/ATR and Chk2 interact with Che-1 and promote its phosphorylation and accumulation in response to DNA damage. These Che-1 modifications induce a specific recruitment of Che-1 on the TP53 and p21 promoters. Interestingly, it has a profound effect on the basal expression of p53, which is preserved following DNA damage. Notably, Che-1 contributes to the maintenance of the G2/M checkpoint induced by DNA damage. These findings identify a mechanism by which checkpoint kinases regulate responses to DNA damage.

Original languageEnglish
Pages (from-to)473-486
Number of pages14
JournalCancer Cell
Volume10
Issue number6
DOIs
Publication statusPublished - Dec 2006

Keywords

  • CELLCYCLE
  • DNA
  • PROTEINS

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

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