MLL (基因)

组蛋白-赖氨酸N-甲基转移酶HRX（英語：Histone-lysine N-methyltransferase HRX）是人体中由MLL（ALL1）基因编码的一种酶。MLL代表髓样/淋巴样，或混合世系白血病。 MLL是一种组蛋白甲基转移酶，被认为是影响基因转录的全局正向调控物。该蛋白属于组蛋白修饰酶类家族，包含了转活化结构域9aaTAD，且参与了对转录记忆的表观遗传学维持。 MLL基因若发生重排（即染色体结构改变造成遗传物质的重新排列）则会导致严重的急性白血病，包括淋巴母细胞性及髓性。该基因亦可能参与了精神分裂症中GAD67表达下调的过程。 现已显示MLL这个基因与HDAC1、PPP1R15A、宿主细胞因子C1、MEN1 RBBP5, ASH2L,、CREB结合蛋白、WDR5 CTBP1及PPIE.之间有着相互作用。 Ziemin-van der Poel S. Identification of a gene, MLL, that spans the breakpoint in 11q23 translocations associated with human leukemias. Proc Natl Acad Sci U S A. January 1992, 88 (23): 10735–9. PMC 53005 . PMID 1720549. doi:10.1073/pnas.88.23.10735.  Piskacek S, Gregor M, Nemethova M, Grabner M, Kovarik P, Piskacek M. Nine-amino-acid transactivation domain: establishment and prediction utilities. Genomics. June 2007, 89 (6): 756–68. PMID 17467953. doi:10.1016/j.ygeno.2007.02.003. ; Piskacek M. Common Transactivation Motif 9aaTAD recruits multiple general co-activators TAF9, MED15, CBP and p300. Nature Precedings: Prepublication research and preliminary findings. November 2009. doi:10.1038/npre.2009.3488.2. ; Piskacek M. 9aaTADs mimic DNA to interact with a pseudo-DNA Binding Domain KIX of Med15 (Molecular Chameleons). Nature Preceedings: Prepublication research and preliminary findings. November 2009. doi:10.1038/npre.2009.3939.1. ; Goto NK, Zor T, Martinez-Yamout M, Dyson HJ, Wright PE. Cooperativity in transcription factor binding to the coactivator CREB-binding protein (CBP). The mixed lineage leukemia protein (MLL) activation domain binds to an allosteric site on the KIX domain. J. Biol. Chem. November 2002, 277 (45): 43168–74. PMID 12205094. doi:10.1074/jbc.M207660200. ; Prasad R, Yano T, Sorio C, Nakamura T, Rallapalli R, Gu Y, Leshkowitz D, Croce CM, Canaani E. Domains with transcriptional regulatory activity within the ALL1 and AF4 proteins involved in acute leukemia. Proc. Natl. Acad. Sci. U.S.A. December 1995, 92 (26): 12160–4. PMC 40316 . PMID 8618864. doi:10.1073/pnas.92.26.12160. ; Ernst P, Wang J, Huang M, Goodman RH, Korsmeyer SJ. MLL and CREB Bind Cooperatively to the Nuclear Coactivator CREB-Binding Protein. Mol. Cell. Biol. April 2001, 21 (7): 2249–58. PMC 86859 . PMID 11259575. doi:10.1128/MCB.21.7.2249-2258.2001.  Guenther MG, Jenner RG, Chevalier B, Nakamura T, Croce CM, Canaani E, Young RA. Global and Hox-specific roles for the MLL1 methyltransferase. Proc. Natl. Acad. Sci. U.S.A. June 2005, 102 (24): 8603–8. PMC 1150839 . PMID 15941828. doi:10.1073/pnas.0503072102.  Huang HS, Matevossian A, Whittle C, Kim SY, Schumacher A, Baker SP, Akbarian S. Prefrontal dysfunction in schizophrenia involves mixed-lineage leukemia 1-regulated histone methylation at GABAergic gene promoters. J. Neurosci. October 2007, 27 (42): 11254–62. PMID 17942719. doi:10.1523/JNEUROSCI.3272-07.2007.  Xia, Zhen-Biao; Anderson Melanie; Diaz Manuel O; Zeleznik-Le Nancy J. MLL repression domain interacts with histone deacetylases, the polycomb group proteins HPC2 and BMI-1, and the corepressor C-terminal-binding protein. Proc. Natl. Acad. Sci. U.S.A. (United States). July 2003, 100 (14): 8342–7. ISSN 0027-8424. PMC 166231 . PMID 12829790. doi:10.1073/pnas.1436338100.  Adler, H T; Chinery R; Wu D Y; Kussick S J; Payne J M; Fornace A J; Tkachuk D C. Leukemic HRX Fusion Proteins Inhibit GADD34-Induced Apoptosis and Associate with the GADD34 and hSNF5/INI1 Proteins. Mol. Cell. Biol. (UNITED STATES). October 1999, 19 (10): 7050–60. ISSN 0270-7306. PMC 84700 . PMID 10490642.  Yokoyama, Akihiko; Wang Zhong; Wysocka Joanna; Sanyal Mrinmoy; Aufiero Deborah J; Kitabayashi Issay; Herr Winship; Cleary Michael L. Leukemia Proto-Oncoprotein MLL Forms a SET1-Like Histone Methyltransferase Complex with Menin To Regulate Hox Gene Expression. Mol. Cell. Biol. (United States). July 2004, 24 (13): 5639–49. ISSN 0270-7306. PMC 480881 . PMID 15199122. doi:10.1128/MCB.24.13.5639-5649.2004.  Goto, Natalie K; Zor Tsaffrir; Martinez-Yamout Maria; Dyson H Jane; Wright Peter E. Cooperativity in transcription factor binding to the coactivator CREB-binding protein (CBP). The mixed lineage leukemia protein (MLL) activation domain binds to an allosteric site on the KIX domain. J. Biol. Chem. (United States). November 2002, 277 (45): 43168–74. ISSN 0021-9258. PMID 12205094. doi:10.1074/jbc.M207660200.  Ernst, P; Wang J; Huang M; Goodman R H; Korsmeyer S J. MLL and CREB Bind Cooperatively to the Nuclear Coactivator CREB-Binding Protein. Mol. Cell. Biol. (United States). April 2001, 21 (7): 2249–58. ISSN 0270-7306. PMC 86859 . PMID 11259575. doi:10.1128/MCB.21.7.2249-2258.2001.  Fair, K; Anderson M; Bulanova E; Mi H; Tropschug M; Diaz M O. Protein Interactions of the MLL PHD Fingers Modulate MLL Target Gene Regulation in Human Cells. Mol. Cell. Biol. (United States). May 2001, 21 (10): 3589–97. ISSN 0270-7306. PMC 100280 . PMID 11313484. doi:10.1128/MCB.21.10.3589-3597.2001.  Marschalek R; Nilson I; Löchner K; Greim, R; Siegler, G; Greil, J; Beck, JD; Fey, GH. The structure of the human ALL-1/MLL/HRX gene. Leuk. Lymphoma. 1998, 27 (5–6): 417–28. PMID 9477123. doi:10.3109/10428199709058308.  Eguchi M, Eguchi-Ishimae M, Greaves M. The role of the MLL gene in infant leukemia. Int. J. Hematol. 2004, 78 (5): 390–401. PMID 14704031. doi:10.1007/BF02983811.  Daser A, Rabbitts TH. Extending the repertoire of the mixed-lineage leukemia gene MLL in leukemogenesis. Genes Dev. 2004, 18 (9): 965–74. PMID 15132992. doi:10.1101/gad.1195504.  Li ZY, Liu DP, Liang CC. New insight into the molecular mechanisms of MLL-associated leukemia. Leukemia. 2005, 19 (2): 183–90. PMID 15618964. doi:10.1038/sj.leu.2403602.  Douet-Guilbert N; Morel F; Le Bris MJ; Sassolas, Bruno; Giroux, Jean-Dominique; De Braekeleer, Marc. Rearrangement of MLL in a patient with congenital acute monoblastic leukemia and granulocytic sarcoma associated with a t(1;11)(p36;q23) translocation. Leuk. Lymphoma. 2005, 46 (1): 143–6. PMID 15621793. doi:10.1080/104281904000010783.  MLL OMIM Entry: （页面存档备份，存于互联网档案馆） MYELOID/LYMPHOID OR MIXED LINEAGE LEUKEMIA GENE; MLL 醫學主題詞表（MeSH）：MLL+protein,+human Gene MLL on the Atlas of Genetics and Oncology