title: Assembly of the SMRT-histone deacetylase 3 repression complex requires the TCP-1 ring complex.
abstract: The acetylation of histone tails is a primary determinant of gene activity. Histone deacetylase 3 (HDAC3) requires the nuclear receptor corepressor SMRT for HDAC enzyme activity. Here we report that HDAC3 interacts with SMRT only after priming by cellular chaperones including the TCP-1 ring complex (TRiC), which is required for proper folding of HDAC3 in an ATP-dependent process. SMRT displaces TRiC from HDAC3, yielding an active HDAC enzyme. The SMRT-HDAC3 repression complex thus joins the VHL-elongin BC tumor suppression complex and the cyclin E-Cdk2 cell cycle regulation complex as critical cellular machines requiring TRiC for proper assembly and function. The strict control of HDAC3 activity underscores the cellular imperative that histone deacetylation occur only in targeted regions of the genome.
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Guenther
authors.forename: Jiujiu
authors.initials: J
authors.lastname: Yu
authors.forename: Gary D
authors.initials: GD
authors.lastname: Kao
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Yen
authors.forename: Mitchell A
authors.initials: MA
authors.lastname: Lazar
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D016367:Baculoviridae / Q000235:genetics / Q000378:metabolism; D016227:Benzoquinones; D002467:Cell Nucleus / Q000378:metabolism; D056404:Chaperonin Containing TCP-1; D018833:Chaperonins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000502:physiology*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047029:Lactams, Macrocyclic; D018613:Microscopy, Confocal; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors; D056971:Nuclear Receptor Co-Repressor 1; D056985:Nuclear Receptor Co-Repressor 2; D011485:Protein Binding / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011809:Quinones / Q000494:pharmacology; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured / Q000378:metabolism; D000099186:Histone Deacetylase 3
chemical_list: D000255:Adenosine Triphosphate; D016227:Benzoquinones; D056404:Chaperonin Containing TCP-1; D018833:Chaperonins; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D006655:Histone Deacetylases; D047029:Lactams, Macrocyclic; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D056985:Nuclear Receptor Co-Repressor 2; D011505:Protein-Tyrosine Kinases; D011809:Quinones; D011994:Recombinant Proteins; D012097:Repressor Proteins; D000099186:Histone Deacetylase 3; C539127:NCOR1 protein, human; C539130:NCOR2 protein, human; C001277:geldanamycin