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Che-1 phosphorylation by ATM/ATR and Chk2 kinases activates p53 transcription and the G2/M checkpoint.
- Source :
-
Cancer cell [Cancer Cell] 2006 Dec; Vol. 10 (6), pp. 473-86. - Publication Year :
- 2006
-
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.
- Subjects :
- Animals
Antineoplastic Agents pharmacology
Ataxia Telangiectasia Mutated Proteins
Cell Division
Checkpoint Kinase 2
Cyclin-Dependent Kinase Inhibitor p21 genetics
DNA Damage
G2 Phase
Humans
Mice
NIH 3T3 Cells
Phosphorylation
Promoter Regions, Genetic
Transcription, Genetic
Apoptosis Regulatory Proteins metabolism
Cell Cycle Proteins physiology
DNA-Binding Proteins physiology
Genes, p53
Protein Serine-Threonine Kinases physiology
Repressor Proteins metabolism
Transcription Factors metabolism
Tumor Suppressor Proteins physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1535-6108
- Volume :
- 10
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Cancer cell
- Publication Type :
- Academic Journal
- Accession number :
- 17157788
- Full Text :
- https://doi.org/10.1016/j.ccr.2006.10.012