title: Structure of AF3p21, a new member of mixed lineage leukemia (MLL) fusion partner proteins-implication for MLL-induced leukemogenesis.
abstract: The Mixed Lineage Leukemia (MLL) gene is frequently rearranged in leukemia, especially in infantile leukemia and therapy-related leukemia. The MLL gene is localized at chromosome 11q23, and is involved in almost all of the chromosomal translocations involving 11q23. Twenty-four fusion partner genes have been identified to date, and the N-terminus of MLL fuses in-frame to the partner genes in all cases. Some of the MLL fusion partner genes encode transcription factors; others encode small GTP binding protein interacting molecules or cytoplasmic proteins, the functions of which are presently unknown. As a result of the diverse features of the MLL fusion partners, the underlying mechanism for leukemogenesis remains obscure. We cloned the MLL fusion partner gene from leukemic cells from a therapy-related leukemia patient with t(3;11)(p21;q23) and designated the gene AF3p21. This patient had a long latency period (9 years) before developing secondary leukemia. The AF3p21 gene encodes a nuclear protein with a molecular mass of 80 kDa, and this protein has SH3 and proline-rich domains. Among MLL fusion partners identified to date, only AF10 and AF17 have a homo-oligomerization domain. AF3p21 also has a homo-oligomerization domain, which was revealed by using a mammalian two-hybrid system. These results suggest that one possible role of the MLL fusion partners is to form an oligomer of truncated MLL. In this review, current knowledge about MLL-involved leukemogenesis is outlined.
authors.affiliation: Department of Pediatrics, Kobe University School of Medicine, Japan. sanoped@kobe-u.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Sano
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002880:Chromosomes, Human, Pair 11; D002893:Chromosomes, Human, Pair 3; D004268:DNA-Binding Proteins / Q000235:genetics; D019281:Dimerization; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D015456:Leukemia, Biphenotypic, Acute / Q000209:etiology* / Q000235:genetics; D009124:Muscle Proteins; D051788:Myeloid-Lymphoid Leukemia Protein; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D017434:Protein Structure, Tertiary; D011519:Proto-Oncogenes; D014157:Transcription Factors; D014178:Translocation, Genetic
chemical_list: C404148:AF3p21-MLL fusion protein, human; D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D009124:Muscle Proteins; C486062:NCKIPSD protein, human; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase