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c-Jun downregulation by HDAC3-dependent transcriptional repression promotes osmotic stress-induced cell apoptosis

Yan Xia1, Ji Wang, Ta-Jen Liu

  • 1Brain Tumor Center and Department of Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.

Molecular Cell
|January 25, 2007
PubMed

Insights

Osmotic stress represses c-Jun via truncated HDAC3, impacting cell survival. Restoring c-Jun levels through exogenous expression suppresses apoptosis, revealing HDAC3

Area of Science:

  • Molecular biology
  • Cellular biology
  • Epigenetics

Background:

  • c-Jun, a key transcription factor in the activating protein 1 (AP-1) family, responds to various stimuli.
  • The regulation of c-Jun by epigenetic modifications, particularly chromatin structure, remains largely uncharacterized.

Purpose of the Study:

  • To investigate the epigenetic regulation of c-Jun during osmotic stress.
  • To elucidate the role of histone deacetylase 3 (HDAC3) in c-Jun transcriptional repression.

Main Methods:

  • Analysis of c-Jun expression under osmotic stress conditions.
  • Investigation of caspase-7 activation pathways, including caspase-8, MEK2, and FAS ligand.
  • Assessment of truncated HDAC3-induced apoptosis and the effect of c-Jun modulation.

Main Results:

  • Osmotic stress leads to transcriptional repression of c-Jun mediated by a truncated HDAC3.
  • Truncated HDAC3 is generated through caspase-7-dependent cleavage at aspartic acid 391.
  • Caspase-7 activation is independent of the mitochondrial pathway but relies on caspase-8, MEK2 activity, and FAS ligand secretion.
  • Exogenous expression of c-Jun suppressed apoptosis induced by truncated HDAC3 or c-Jun deficiency during osmotic stress.

Conclusions:

  • HDAC3-dependent transcriptional repression of c-Jun is a significant mechanism regulating cell survival and apoptosis.
  • The interplay between HDAC3, caspases, and c-Jun is crucial in cellular responses to osmotic stress.

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