AI Article Synopsis
- c-Jun, a key transcription factor in the AP-1 family, is repressed during osmotic stress due to a truncated form of HDAC3 created by caspase-7 cleavage.
- Activation of caspase-7 occurs independently of cytochrome c, requiring the prior activation of caspase-8 and MEK2 activity.
- The study suggests that the downregulation of c-Jun through HDAC3 contributes to cell survival and apoptosis regulation during osmotic stress.
Article Abstract
c-Jun, a major transcription factor in the activating protein 1 (AP-1) family of regulatory proteins, is activated by many physiologic and pathologic stimuli. However, whether c-jun is regulated by epigenetic modification of chromatin structure is not clear. We showed here that c-jun was transcriptionally repressed in response to osmotic stress via a truncated HDAC3 generated by caspase-7-dependent cleavage at aspartic acid 391. The activation of caspase-7, which is independent of cytochrome c release and activation of caspase-9 and caspase-12, depends on activation of caspase-8, which in turn requires MEK2 activity and secretion of FAS ligand. The cell apoptosis induced by the truncated HDAC3 or enhanced by c-Jun deficiency during osmotic stress was suppressed by exogenous expression of c-Jun, indicating that the downregulation of c-Jun by HDAC3-dependent transcriptional repression plays a role in regulating cell survival and apoptosis.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1829326 | PMC |
| http://dx.doi.org/10.1016/j.molcel.2007.01.005 | DOI Listing |
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