G betagamma binds histone deacetylase 5 (HDAC5) and inhibits its transcriptional co-repression activity.

Spiegelberg BD, Hamm HE
J Biol Chem. 2005 280 (50): 41769-76

PMID: 16221676 · DOI:10.1074/jbc.M504066200

In a yeast two-hybrid screen designed to identify novel effectors of the G betagamma subunit of heterotrimeric G proteins, we found that G betagamma binds to histone deacetylase 5 (HDAC5), an enzyme involved in a pathway not previously recognized to be directly impacted by G proteins. Formation of the G beta1gamma2-HDAC5 complex in mammalian cells can be blocked by overexpression of G alpha(o), and this inhibition is relieved by activation of alpha2A-adrenergic receptor, suggesting that the interaction occurs in a signal-dependent manner. The C-terminal domain of HDAC5 binds directly to G betagamma through multiple motifs, and overexpression of this domain mimics the C terminus of G protein-coupled receptor kinase 2, a known G betagamma scavenger, in its ability to inhibit the G betagamma/HDAC5 interaction. The C terminus of HDAC4 shares significant similarity with that of HDAC5, and accordingly, HDAC4 is also able to form complexes with G beta1gamma2 in cultured cells, suggesting that the C-terminal domain of class II HDACs is a general G betagamma binding motif. Activation of a G(i/o)-coupled receptor results in a time-dependent activation of MEF2C, an HDAC5-regulated transcription factor, whereas inhibition of the interaction with a G betagamma scavenger inhibits MEF2C activity, suggesting a reduced potency of HDAC5-mediated inhibition. Taken together, these data imply that HDAC5 and possibly other class II HDACs can be added to the growing list of G betagamma effectors.

MeSH Terms (24)

Amino Acid Motifs Animals Blotting, Western Cattle Cell Line Genes, Reporter GTP-Binding Protein beta Subunits GTP-Binding Protein gamma Subunits Histone Deacetylases Humans Immunoprecipitation Mice Plasmids Protein Binding Protein Structure, Tertiary Rats Rats, Sprague-Dawley Receptors, Adrenergic, alpha-2 Repressor Proteins Signal Transduction Time Factors Transcription, Genetic Transfection Two-Hybrid System Techniques

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