title: Transcriptional activation by MLL fusion proteins in leukemogenesis.
abstract: Chromosomal translocations involving the mixed lineage leukemia (MLL) gene cause aggressive leukemia. Fusion proteins of MLL and a component of the AF4 family/ENL family/P-TEFb complex (AEP) are responsible for two-thirds of MLL-associated leukemia cases. MLL-AEP fusion proteins trigger aberrant self-renewal of hematopoietic progenitors by constitutively activating self-renewal-related genes. MLL-AEP fusion proteins activate transcription initiation by loading the TATA-binding protein (TBP) to the TATA element via selectivity factor 1. Although AEP retains transcription elongation and mediator recruiting activities, the rate-limiting step activated by MLL-AEP fusion proteins appears to be the TBP-loading step. This is contrary to prevailing views, in which the recruitment of transcription elongation activities are emphasized. Here, I review recent advances towards elucidating the mechanisms underlying gene activation by MLL-AEP fusion proteins in leukemogenesis.
authors.affiliation: Department of Hematology and Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan; Division of Hematological Malignancy, National Cancer Center Research Institute, Tokyo, Japan. Electronic address: yokoyama@kuhp.kyoto-u.ac.jp.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yokoyama
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007938:Leukemia / Q000235:genetics* / Q000378:metabolism*; D051788:Myeloid-Lymphoid Leukemia Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D015533:Transcriptional Activation
chemical_list: D015514:Oncogene Proteins, Fusion; D051788:Myeloid-Lymphoid Leukemia Protein