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The prolyl isomerase Pin1 affects Che-1 stability in response to apoptotic DNA damage.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2007 Jul 06; Vol. 282 (27), pp. 19685-91. Date of Electronic Publication: 2007 Apr 27. - Publication Year :
- 2007
-
Abstract
- We have previously demonstrated that DNA damage leads to stabilization and accumulation of Che-1, an RNA polymerase II-binding protein that plays an important role in transcriptional activation of p53 and in maintenance of the G(2)/M checkpoint. Here we show that Che-1 is down-regulated during the apoptotic process. We found that the E3 ligase HMD2 physically and functionally interacts with Che-1 and promotes its degradation via the ubiquitin-dependent proteasomal system. Furthermore, we found that in response to apoptotic stimuli Che-1 interacts with the peptidyl-prolyl isomerase Pin1 and that conformational changes generated by Pin1 are required for Che-1/HDM2 interaction. Notably, a Che-1 mutant lacking the capacity to bind Pin1 exhibits an increased half-life and this correlates with a diminished apoptosis in response to genotoxic stress. Our results establish Che-1 as a new Pin1 and HDM2 target and confirm its important role in the cellular response to DNA damage.
- Subjects :
- Animals
Apoptosis Regulatory Proteins genetics
Cell Division
Cell Line, Tumor
Down-Regulation
G2 Phase
Humans
Mice
Mutation
NIMA-Interacting Peptidylprolyl Isomerase
Peptidylprolyl Isomerase genetics
Proteasome Endopeptidase Complex genetics
Proteasome Endopeptidase Complex metabolism
Proto-Oncogene Proteins c-mdm2 genetics
Proto-Oncogene Proteins c-mdm2 metabolism
Repressor Proteins genetics
Transcription Factors genetics
Ubiquitin metabolism
Ubiquitin-Protein Ligases genetics
Ubiquitin-Protein Ligases metabolism
Apoptosis
Apoptosis Regulatory Proteins metabolism
DNA Damage
Peptidylprolyl Isomerase metabolism
Repressor Proteins metabolism
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 282
- Issue :
- 27
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 17468107
- Full Text :
- https://doi.org/10.1074/jbc.M610282200