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

Francesca De Nicola, Tiziana Bruno, Simona Iezzi, Monica Di Padova, Aristide Floridi, Claudio Passananti, Giannino Del Sal, Maurizio Fanciulli

Research output: Contribution to journalArticlepeer-review


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 G2/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.

Original languageEnglish
Pages (from-to)19685-19691
Number of pages7
JournalJournal of Biological Chemistry
Issue number27
Publication statusPublished - Jul 6 2007

ASJC Scopus subject areas

  • Biochemistry


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