Document Detail


The STAGA subunit ADA2b is an important regulator of human GCN5 catalysis.
MedLine Citation:
PMID:  18936164     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Human STAGA is a multisubunit transcriptional coactivator containing the histone acetyltransferase GCN5L. Previous studies of the related yeast SAGA complex have shown that the yeast Gcn5, Ada2, and Ada3 components form a heterotrimer that is important for the enzymatic function of SAGA. Here, we report that ADA2a and ADA2b, two human homologues of yeast Ada2, each have the ability to form a heterotrimer with ADA3 and GCN5L but that only the ADA2b homologue is found in STAGA. By comparing the patterns of acetylation of several substrates, we found context-dependent requirements for ADA2b and ADA3 for the efficient acetylation of histone tails by GCN5. With human proteins, unlike yeast proteins, the acetylation of free core histones by GCN5 is unaffected by ADA2b or ADA3. In contrast, the acetylation of mononucleosomal substrates by GCN5 is enhanced by ADA2b, with no significant additional effect of ADA3, and the efficient acetylation of nucleosomal arrays (chromatin) by GCN5 requires both ADA2b and ADA3. Thus, ADA2b and ADA3 appear to act at two different levels of histone organization within chromatin to facilitate GCN5 function. Interestingly, although ADA2a forms a complex(es) with GCN5 and ADA3 both in vitro and in vivo, ADA2a-containing complexes are unable to acetylate nucleosomal H3. We have also shown the preferential recruitment of ADA2b, relative to ADA2a, to p53-dependent genes. This finding indicates that the previously demonstrated presence and function of GCN5 on these promoters reflect the action of STAGA and that the ADA2a and ADA2b paralogues have nonredundant functional roles.
Authors:
Armin M Gamper; Jaehoon Kim; Robert G Roeder
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-10-20
Journal Detail:
Title:  Molecular and cellular biology     Volume:  29     ISSN:  1098-5549     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2008-12-16     Completed Date:  2009-01-14     Revised Date:  2011-10-10    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  266-80     Citation Subset:  IM    
Affiliation:
Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10021, USA.
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MeSH Terms
Descriptor/Qualifier:
Acetylation
Adaptor Proteins, Signal Transducing / chemistry,  metabolism*
Amino Acid Sequence
Carrier Proteins / chemistry,  metabolism*
Catalysis
Catalytic Domain
Cell Line, Tumor
Histone Acetyltransferases / metabolism
Histones / metabolism
Humans
Molecular Sequence Data
Multiprotein Complexes / metabolism*
Nucleosomes / metabolism
Promoter Regions, Genetic
Protein Binding
Protein Structure, Tertiary
Protein Subunits / metabolism*
Transcription Factors / chemistry,  metabolism*
Tumor Suppressor Protein p53 / genetics
p300-CBP Transcription Factors / metabolism*
Grant Support
ID/Acronym/Agency:
CA113822/CA/NCI NIH HHS; CA129325/CA/NCI NIH HHS; DK071900/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Carrier Proteins; 0/Histones; 0/Multiprotein Complexes; 0/Nucleosomes; 0/Protein Subunits; 0/TADA2A protein, human; 0/TADA2B protein, human; 0/TADA3 protein, human; 0/Transcription Factors; 0/Tumor Suppressor Protein p53; EC 2.3.1.48/Histone Acetyltransferases; EC 2.3.1.48/p300-CBP Transcription Factors; EC 2.3.1.48/p300-CBP-associated factor
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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