Mixed lineage leukemia: a structure-function perspective of the MLL1 protein.
Several acute lymphoblastic and myelogenous leukemias are correlated with alterations in the human mixed lineage leukemia protein-1 (MLL1) gene. MLL1 is a member of the evolutionarily conserved SET1 family of histone H3 lysine 4 (H3K4) methyltransferases, which are required for the regulation of distinct groups of developmentally regulated genes in metazoans. Despite the important biological role of SET1 family enzymes and their involvement in human leukemias, relatively little is understood about how these enzymes work. Here we review several recent structural and biochemical studies that are beginning to shed light on the molecular mechanisms for the regulation of H3K4 methylation by the human MLL1 enzyme.
Department of Biology, Syracuse University, Syracuse, NY 13244, USA. mscosgro@syr.edu
Michael S
MS
Cosgrove
Anamika
A
Patel
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D005544:Forecasting; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D051788:Myeloid-Lymphoid Leukemia Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary / Q000235:genetics; D013329:Structure-Activity Relationship
D006657:Histones; C497422:KMT2A protein, human; D008024:Ligands; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine