PubMed Journals: Mol Cell Biol

  Source:		PMID: 14701748

    		Mol Cell Biol. 2004 Jan;24(2):765-73.
			Negative regulation of histone deacetylase 8
			activity by cyclic AMP-dependent protein
			kinase A.

			Lee H(1), Rezai-Zadeh N, Seto E.

			Author Information
			H. Lee Moffitt Cancer Center and Research Institute,
			12902 Magnolia Drive, Tampa, FL 33612, USA.

			Histone deacetylases (HDACs) are enzymes
			that catalyze the removal of acetyl groups
			from lysine residues of histone and nonhistone
			proteins. Recent studies suggest that they
			are key regulators of many cellular events,
			including cell proliferation and cancer
			development. Human class I HDACs possess
			homology to the yeast RPD3 protein and include
			HDAC1, HDAC2, HDAC3, and HDAC8. While HDAC1,
			HDAC2, and HDAC3 have been characterized
			extensively, almost nothing is known about
			HDAC8. Here we report that HDAC8 is phosphorylated
			by cyclic AMP-dependent protein kinase A
			(PKA) in vitro and in vivo. The PKA phosphoacceptor
			site of HDAC8 is Ser(39), a nonconserved
			residue among class I HDACs. Mutation of
			Ser(39) to Ala enhances the deacetylase
			activity of HDAC8. In contrast, mutation
			of Ser(39) to Glu or induction of HDAC8
			phosphorylation by forskolin, a potent activator
			of adenyl cyclase, decreases HDAC8's enzymatic
			activity. Remarkably, inhibition of HDAC8
			activity by hyperphosphorylation leads to
			hyperacetylation of histones H3 and H4,
			suggesting that PKA-mediated phosphorylation
			of HDAC8 plays a central role in the overall
			acetylation status of histones.

			PMCID: PMC343812 PMID: 14701748 [Indexed
			for MEDLINE]

     			                         Tweet       Print