First Author | Bruno T | Year | 2006 |
Journal | Cancer Cell | Volume | 10 |
Issue | 6 | Pages | 473-86 |
PubMed ID | 17157788 | Mgi Jnum | J:172986 |
Mgi Id | MGI:5009399 | Doi | 10.1016/j.ccr.2006.10.012 |
Citation | Bruno T, et al. (2006) Che-1 phosphorylation by ATM/ATR and Chk2 kinases activates p53 transcription and the G2/M checkpoint. Cancer Cell 10(6):473-86 |
abstractText | 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. |