HDAC3 is linked to cell cycle machinery in MiaPaCa2 cells by regulating transcription of skp2

Cell Prolif. 2007 Aug;40(4):522-31. doi: 10.1111/j.1365-2184.2007.00454.x.


Objective: Histone deacetylases (HDACs) have been linked to cell cycle control in various models, involving regulation of the cyclin-dependent kinase inhibitor p27(Kip1).

Results: Here, we demonstrate that HDAC inhibition by trichostatin A reduces S-phase kinase-associated protein 2 mRNA and protein abundance. Furthermore, in contrast to HDAC1, recruited to the skp2 promoter in the G(0) phase, HDAC3 is bound in early S phase. Activating function of HDAC3 towards the skp2 gene has been validated using RNA interference techniques. siRNAs, targeting HDAC3 specifically, reduced skp2 transcription.

Conclusion: These findings propose that the skp2 gene is a novel target of HDAC3, mediating cell cycle control and oncogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation*
  • Histone Deacetylase Inhibitors
  • Histone Deacetylases / metabolism*
  • Humans
  • Hydroxamic Acids / pharmacology
  • Promoter Regions, Genetic
  • RNA, Messenger / metabolism
  • S Phase / genetics*
  • S-Phase Kinase-Associated Proteins / biosynthesis
  • S-Phase Kinase-Associated Proteins / genetics*
  • Transcription, Genetic


  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • RNA, Messenger
  • S-Phase Kinase-Associated Proteins
  • trichostatin A
  • Histone Deacetylases
  • histone deacetylase 3