The prolyl isomerase Pin1 affects Che-1 stability in response to apoptotic DNA damage.

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.
Mesh Terms:
Animals, Apoptosis, Apoptosis Regulatory Proteins, Cell Division, Cell Line, Tumor, DNA Damage, Down-Regulation, G2 Phase, Humans, Mice, Mutation, Peptidylprolyl Isomerase, Proteasome Endopeptidase Complex, Proto-Oncogene Proteins c-mdm2, Repressor Proteins, Transcription Factors, Ubiquitin, Ubiquitin-Protein Ligases
J. Biol. Chem.
Date: Jul. 06, 2007
Download Curated Data For This Publication
140890
Switch View:
  • Interactions 3
  • PTM Genes 1