Differential association of products of alternative transcripts of the candidate tumor suppressor ING1 with the mSin3/HDAC1 transcriptional corepressor complex.
The candidate tumor suppressor ING1 was identified in a genetic screen aimed at isolation of human genes whose expression is suppressed in cancer cells. It may function as a negative growth regulator in the p53 signal transduction pathway. However, its molecular mechanism is not clear. The ING1 locus encodes alternative transcripts of p47(ING1a), p33(ING1b), and p24(ING1c). Here we report differential association of protein products of ING1 with the mSin3 transcriptional corepressor complex. p33(ING1b) associates with Sin3, SAP30, HDAC1, RbAp48, and other proteins, to form large protein complexes, whereas p24(ING1c) does not. The ING1 immune complexes are active in deacetylating core histones in vitro, and p33(ING1b) is functionally associated with HDAC1-mediated transcriptional repression in transfected cells. Our data provide basis for a p33(ING1b)-specific molecular mechanism for the function of the ING1 locus.
Skowyra
D
D
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Zeremski
M
M
Neznanov
N
N
Li
M
M
Choi
Y
Y
Uesugi
M
M
Hauser
C A
CA
Gu
W
W
Gudkov
A V
AV
Qin
J
J
D016475:3T3 Cells; D017398:Alternative Splicing; D000818:Animals; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D016147:Genes, Tumor Suppressor; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000378:metabolism*; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D051379:Mice; D009687:Nuclear Proteins; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D012097:Repressor Proteins / Q000378:metabolism*; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C501503:ING1 protein, human; C501505:Ing1 protein, mouse; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D056264:Sin3 Histone Deacetylase and Corepressor Complex