MLL 植物同源结构域（PHD）指蛋白的相互作用调节人类细胞中 MLL 靶基因的调控。
Protein interactions of the MLL PHD fingers modulate MLL target gene regulation in human cells.
作者信息
Fair K, Anderson M, Bulanova E, Mi H, Tropschug M, Diaz M O
机构信息
Cancer Center, Medical Center, Loyola University-Chicago, Maywood, Illinois 60153.
出版信息
Mol Cell Biol. 2001 May;21(10):3589-97. doi: 10.1128/MCB.21.10.3589-3597.2001.
Abstract
The PHD fingers of the human MLL and Drosophila trx proteins have strong amino acid sequence conservation but their function is unknown. We have determined that these fingers mediate homodimerization and binding of MLL to Cyp33, a nuclear cyclophilin. These two proteins interact in vitro and in vivo in mammalian cells and colocalize at specific nuclear subdomains. Overexpression of the Cyp33 protein in leukemia cells results in altered expression of HOX genes that are targets for regulation by MLL. These alterations are suppressed by cyclosporine and are not observed in cell lines that express a mutant MLL protein without PHD fingers. These results suggest that binding of Cyp33 to MLL modulates its effects on the expression of target genes.
摘要
人类MLL蛋白和果蝇trx蛋白的PHD指结构域具有很强的氨基酸序列保守性，但其功能尚不清楚。我们已经确定，这些指结构域介导MLL的同二聚化以及MLL与核亲环蛋白Cyp33的结合。这两种蛋白在体外以及哺乳动物细胞的体内相互作用，并在特定的核亚结构域共定位。白血病细胞中Cyp33蛋白的过表达导致HOX基因表达改变，而HOX基因是MLL调控的靶标。这些改变被环孢素抑制，并且在表达没有PHD指结构域的突变MLL蛋白的细胞系中未观察到。这些结果表明，Cyp33与MLL的结合调节了其对靶基因表达的影响。
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本文引用的文献
1
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Genes Chromosomes Cancer. 2000 Dec;29(4):333-8.
2
Cyclophilin A and Ess1 interact with and regulate silencing by the Sin3-Rpd3 histone deacetylase.亲环蛋白A和Ess1与Sin3-Rpd3组蛋白去乙酰化酶相互作用并调节基因沉默。
EMBO J. 2000 Jul 17;19(14):3739-49. doi: 10.1093/emboj/19.14.3739.
3
Self-association of the SET domains of human ALL-1 and of Drosophila TRITHORAX and ASH1 proteins.人类ALL-1以及果蝇三体胸节蛋白和ASH1蛋白的SET结构域的自我缔合。
Oncogene. 2000 Jan 20;19(3):351-7. doi: 10.1038/sj.onc.1203307.
4
Mammalian Trithorax and polycomb-group homologues are antagonistic regulators of homeotic development.哺乳动物的三胸节同源物和多梳蛋白家族同源物是同源异形发育的拮抗调节因子。
Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14372-7. doi: 10.1073/pnas.96.25.14372.
5
SIN, a novel Drosophila protein that associates with the RNA binding protein sex-lethal.SIN，一种与RNA结合蛋白性致死因子相关的新型果蝇蛋白。
Gene. 1999 Sep 17;237(2):421-8. doi: 10.1016/s0378-1119(99)00303-0.
6
MLL2: A new mammalian member of the trx/MLL family of genes.MLL2：trx/MLL基因家族的一个新的哺乳动物成员。
Genomics. 1999 Jul 15;59(2):187-92. doi: 10.1006/geno.1999.5860.
7
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Oncogene. 1998 Aug 27;17(8):1019-26. doi: 10.1038/sj.onc.1202006.
8
Evolutionary conservation and tissue-specific processing of Hoxa 11 antisense transcripts.Hoxa 11反义转录本的进化保守性与组织特异性加工
Mamm Genome. 1998 Oct;9(10):799-806. doi: 10.1007/s003359900870.
9
Point mutations in v-Myb disrupt a cyclophilin-catalyzed negative regulatory mechanism.v-Myb中的点突变破坏了亲环蛋白催化的负调控机制。
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10
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