Che-1 phosphorylation by ATM/ATR and Chk2 kinases activates p53 transcription and the G2/M checkpoint.
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.
Mesh Terms:
Animals, Antineoplastic Agents, Apoptosis Regulatory Proteins, Cell Cycle Proteins, Cell Division, Cyclin-Dependent Kinase Inhibitor p21, DNA Damage, DNA-Binding Proteins, G2 Phase, Genes, p53, Humans, Mice, NIH 3T3 Cells, Phosphorylation, Promoter Regions, Genetic, Protein-Serine-Threonine Kinases, Repressor Proteins, Transcription Factors, Transcription, Genetic, Tumor Suppressor Proteins
Animals, Antineoplastic Agents, Apoptosis Regulatory Proteins, Cell Cycle Proteins, Cell Division, Cyclin-Dependent Kinase Inhibitor p21, DNA Damage, DNA-Binding Proteins, G2 Phase, Genes, p53, Humans, Mice, NIH 3T3 Cells, Phosphorylation, Promoter Regions, Genetic, Protein-Serine-Threonine Kinases, Repressor Proteins, Transcription Factors, Transcription, Genetic, Tumor Suppressor Proteins
Cancer Cell
Date: Dec. 01, 2006
PubMed ID: 17157788
View in: Pubmed Google Scholar
Download Curated Data For This Publication
126684
Switch View:
- Interactions 3