Differential association of products of alternative transcripts of the candidate tumor suppressor ING1 with the mSin3/HDAC1 transcriptional corepressor complex

被引:120
作者
Skowyra, D
Zeremski, M
Neznanov, N
Li, MY
Choi, YM
Uesugi, M
Hauser, CA
Gu, W
Gudkov, AV
Qin, J [1 ]
机构
[1] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA
[2] Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA
[3] Univ Illinois, Coll Med, Dept Mol Genet, Chicago, IL 60607 USA
[4] Columbia Univ Coll Phys & Surg, Inst Canc Genet, New York, NY 10032 USA
[5] Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA
[6] Burnham Inst, La Jolla, CA 92037 USA
关键词
D O I
10.1074/jbc.M007664200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 HDAC-1-mediated transcriptional repression in transfected cells, Our data provide basis for a p33(ING1b)-specific molecular mechanism for the function of the ING1 locus.
引用
收藏
页码:8734 / 8739
页数:6
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