Back to Search
Start Over
Che-1: a new effector of checkpoints signaling.
- Source :
-
Cell cycle (Georgetown, Tex.) [Cell Cycle] 2007 Apr 01; Vol. 6 (7), pp. 804-6. Date of Electronic Publication: 2007 Apr 22. - Publication Year :
- 2007
-
Abstract
- 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.
- Subjects :
- Animals
Apoptosis Regulatory Proteins genetics
E2F Transcription Factors genetics
Gene Expression Regulation, Neoplastic genetics
Humans
Regulatory Elements, Transcriptional genetics
Repressor Proteins genetics
Transcription Factors genetics
Tumor Suppressor Protein p53 genetics
Apoptosis genetics
Apoptosis Regulatory Proteins physiology
Cell Transformation, Neoplastic genetics
Genes, cdc physiology
Repressor Proteins physiology
Signal Transduction genetics
Transcription Factors physiology
Tumor Suppressor Protein p53 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1551-4005
- Volume :
- 6
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Cell cycle (Georgetown, Tex.)
- Publication Type :
- Academic Journal
- Accession number :
- 17377493
- Full Text :
- https://doi.org/10.4161/cc.6.7.4043