title: Menin as a hub controlling mixed lineage leukemia.
abstract: Mixed lineage leukemia (MLL) fusion protein (FP)-induced acute leukemia is highly aggressive and often refractory to therapy. Recent progress in the field has unraveled novel mechanisms and targets to combat this disease. Menin, a nuclear protein, interacts with wild-type (WT) MLL, MLL-FPs, and other partners such as the chromatin-associated protein LEDGF and the transcription factor C-Myb to promote leukemogenesis. The newly solved co-crystal structure illustrating the menin-MLL interaction, coupled with the role of menin in recruiting both WT MLL and MLL-FPs to target genes, highlights menin as a scaffold protein and a central hub controlling this type of leukemia. The menin/WT MLL/MLL-FP hub may also cooperate with several signaling pathways, including Wnt, GSK3, and bromodomain-containing Brd4-related pathways to sustain MLL-FP-induced leukemogenesis, revealing new therapeutic targets to improve the treatment of MLL-FP leukemias.
authors: Department of Cancer Biology, Abramson Family Cancer Research Institute, Abramson Cancer Center, The University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
authors: Austin T
authors: AT
authors: Thiel
authors: Jing
authors: J
authors: Huang
authors: Ming
authors: M
authors: Lei
authors: Xianxin
authors: X
authors: Hua
mesh_terms: D000107:Acetylation; D018797:Cell Cycle Proteins; D015973:Gene Expression Regulation, Leukemic; D006657:Histones / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015456:Leukemia, Biphenotypic, Acute / Q000378:metabolism* / Q000473:pathology; D051788:Myeloid-Lymphoid Leukemia Protein / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D025941:Protein Interaction Mapping; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D060449:Wnt Signaling Pathway; D000092468:Bromodomain Containing Proteins
chemical_list: D018797:Cell Cycle Proteins; D006657:Histones; D018398:Homeodomain Proteins; D051788:Myeloid-Lymphoid Leukemia Protein; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; C441289:BRD4 protein, human; D000092468:Bromodomain Containing Proteins; C105373:MEN1 protein, human; C097899:homeobox protein HOXA9