MLL (基因)

髓样/淋巴样或混合世系白血病（三胸同源物，果蝇）
	PDB rendering based on 2j2s.
有效结构
PDB	直系同源检索：PDBe, RCSB
PDB查询代码列表
	2AGH, 2J2S, 2JYI, 2KKF, 2KU7, 2KYU, 2LXS, 2LXT, 2W5Y, 2W5Z, 3EG6, 3EMH, 3LQH, 3LQI, 3LQJ, 3P4F, 3U85, 3U88, 4ESG, 4GQ6
标识
代号	MLL; ALL-1; CXXC7; HRX; HTRX1; KMT2A; MLL/GAS7; MLL1A; TET1-MLL; TRX1; WDSTS
扩展标识	遗传学：159555 鼠基因：96995 同源基因：4338 ChEMBL: 1293299 GeneCards: MLL Gene
EC編號	2.1.1.43
基因本体论描述
分子功能	· AT DNA binding; · sequence-specific DNA binding transcription factor activity; · protein binding; · zinc ion binding; · histone methyltransferase activity (H3-K4 specific); · identical protein binding; · protein homodimerization activity; · transcription regulatory region DNA binding; · unmethylated CpG binding; · histone acetyl-lysine binding;
细胞成分	· nucleus; · histone methyltransferase complex; · MLL1 complex;
生物过程	· transcription from RNA polymerase II promoter; · protein complex assembly; · apoptotic process; · positive regulation of transporter activity; · embryonic hemopoiesis; · histone H4-K16 acetylation; · positive regulation of transcription, DNA-dependent; · positive regulation of transcription from RNA polymerase II promoter; · histone H3-K4 methylation; · histone H3-K4 trimethylation; · positive regulation of cellular response to drug;
	Sources: Amigo / QuickGO
RNA表达模式
	更多表达数据
直系同源体
	查; 论; 编;

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^[1]。

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^[2]，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^[3]。该基因亦可能参与了精神分裂症中GAD67表达下调的过程^[4]。

交互作用编辑

现已显示MLL这个基因与HDAC1^[5]、PPP1R15A^[6]、宿主细胞因子C1^[7]、MEN1^[7] RBBP5,^[7] ASH2L,^[7]、CREB结合蛋白^[8]^[9]、WDR5^[7] CTBP1^[5]及PPIE.^[10]之间有着相互作用。

参考文献编辑

^ 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.
^ ^5.0 ^5.1 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.
^ ^7.0 ^7.1 ^7.2 ^7.3 ^7.4 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.

深入阅读编辑

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.

外部链接编辑

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

[pmid1720549-1] 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.

[9aaTAD-2] 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.

[pmid15941828-3] 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.

[pmid17942719-4] 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.

[pmid12829790-5] 5.0 ^5.1 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.

[pmid10490642-6] 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.

[pmid15199122-7] 7.0 ^7.1 ^7.2 ^7.3 ^7.4 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.

[pmid12205094-8] 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.

[pmid11259575-9] 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.

[pmid11313484-10] 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.

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MLL (基因)

交互作用 编辑

参考文献 编辑

深入阅读 编辑

外部链接 编辑

交互作用编辑

参考文献编辑

深入阅读编辑

外部链接编辑