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Cell Prolif. 2007 Aug;40(4):522-31.

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

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Department of Internal Medicine II, Technical University of Munich, Munich, Germany.



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


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.


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

[Indexed for MEDLINE]

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