Abstract
Histone deacetylase 9 (HDAC9), like most Class II HDACs, catalyzes the removal of acetyl moieties from the ε-amino groups of conserved lysine residues in the N-terminal tail of histones. Biologically, HDAC9 regulates a wide variety of normal and abnormal physiological functions, including cardiac growth, T-regulatory cell function, neuronal disorders, muscle differentiation, development, and cancer. In a biochemical approach to identify non-histone substrates of HDAC9, we found that HDAC9 co-purifies specifically with the ataxia telangiectasia group D-complementing (ATDC; also called TRIM29) protein. HDAC9 deacetylates ATDC, alters the ability of ATDC to associate with p53, and consequently inhibits the cell proliferation-promoting activity of ATDC. These results implicate the importance of non-histone deacetylation by HDAC9 and confirm and further extend the multifunctions of this Class II deacetylase.
Highlights
The myocyte enhancer-binding factor 2-interacting transcriptional repressor (MITR), which possesses amino acid sequence similarity to Class II histone deacetylases (HDACs) but lacks an HDAC catalytic domain, was first discovered as a binding partner and a negative regulator of MEF-2 in a yeast two-hybrid screen [3]
We found that one of the proteins that associates with Histone deacetylase 9 (HDAC9) is ataxia telangiectasia group D-complementing (ATDC)
ATDC Interacts with HDAC9—To further understand the functions and mechanisms of action of HDAC9, we sought to identify proteins that associate with HDAC9
Summary
The myocyte enhancer-binding factor 2-interacting transcriptional repressor (MITR), which possesses amino acid sequence similarity to Class II HDACs but lacks an HDAC catalytic domain, was first discovered as a binding partner and a negative regulator of MEF-2 (myocyte enhancer-binding factor 2) in a yeast two-hybrid screen [3]. Deacetylation of ATDC by HDAC9 changes the ability of ATDC to bind p53 and affects expression of p53-regulated genes and reverses the cell proliferation-promoting activity of ATDC. After two rounds of the affinity purification, the gel pattern, based on silver staining coupled with Western blot analyses (using antibodies directed against proteins known to interact with HDAC9 and MITR) indicated a distinct novel HDAC9 complex.
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