Protein interactions of the MLL PHD fingers modulate MLL target gene regulation in human cells.
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.
Mesh Terms:
Amino Acid Sequence, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Gene Targeting, Humans, K562 Cells, Molecular Sequence Data, Myeloid-Lymphoid Leukemia Protein, Protein Binding, Proto-Oncogenes, Transcription Factors, Zinc Fingers
Amino Acid Sequence, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Gene Targeting, Humans, K562 Cells, Molecular Sequence Data, Myeloid-Lymphoid Leukemia Protein, Protein Binding, Proto-Oncogenes, Transcription Factors, Zinc Fingers
Mol. Cell. Biol.
Date: May. 01, 2001
PubMed ID: 11313484
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