Che-1: A New Effector of Checkpoints Signaling

Aristide Floridi and Maurizio Fanciulli

volume 6 | issue 7

1 April 2007
Pages: 804 - 806

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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.

Authors

Aristide Floridi

1Department of Experimental Medicine; University of L'Aquila; L'Aquila, Italy

Maurizio Fanciulli

Regina Elena Cancer Institute; Rome, Italy

We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link: