Human ING1 proteins differentially regulate histone acetylation.
ING1 proteins are nuclear, growth inhibitory, and regulate apoptosis in different experimental systems. Here we show that similar to their yeast homologs, human ING1 proteins interact with proteins associated with histone acetyltransferase (HAT) activity, such as TRRAP, PCAF, CBP, and p300. Human ING1 immunocomplexes contain HAT activity, and overexpression of p33(ING1b), but not of p47(ING1a), induces hyperacetylation of histones H3 and H4, in vitro and in vivo at the single cell level. p47(ING1a) inhibits histone acetylation in vitro and in vivo and binds the histone deacetylase HDAC1. Finally, we present evidence indicating that p33(ING1b) affects the degree of physical association between proliferating cell nuclear antigen (PCNA) and p300, an association that has been proposed to link DNA repair to chromatin remodeling. Together with the finding that human ING1 proteins bind PCNA in a DNA damage-dependent manner, these data suggest that ING1 proteins provide a direct linkage between DNA repair, apoptosis, and chromatin remodeling via multiple HAT.ING1.PCNA protein complexes.
Vieyra
Diego
D
Department of Biochemistry, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
Loewith
Robbie
R
Scott
Michelle
M
Bonnefin
Paul
P
Boisvert
Francois-Michel
FM
Cheema
Parneet
P
Pastyryeva
Svitlana
S
Meijer
Maria
M
Johnston
Randal N
RN
Bazett-Jones
David P
DP
McMahon
Steven
S
Cole
Michael D
MD
Young
Dallan
D
Riabowol
Karl
K
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology; D018797:Cell Cycle Proteins; D002460:Cell Line; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D016147:Genes, Tumor Suppressor; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism*; D006801:Humans; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011506:Proteins / Q000378:metabolism* / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D006657:Histones; C501503:ING1 protein, human; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins; D025521:Tumor Suppressor Proteins; D000123:Acetyltransferases; D051548:Histone Acetyltransferases