Fair K, Anderson M, Bulanova E, Mi H, Tropschug M, Diaz M O
Cancer Center, Medical Center, Loyola University-Chicago, Maywood, Illinois 60153.
Mol Cell Biol. 2001 May;21(10):3589-97. doi: 10.1128/MCB.21.10.3589-3597.2001.
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.
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。
