MLL (基因)

位於11號人類染色體的基因

組蛋白-賴氨酸N-甲基轉移酶HRX(英語:Histone-lysine N-methyltransferase HRX)是人體中由MLL(ALL1)基因編碼的一種。MLL代表髓樣/淋巴樣,或混合世系白血病[1]

髓樣/淋巴樣或混合世系白血病(三胸同源物,果蠅)
PDB rendering based on 2j2s.
有效結構
PDB 直系同源檢索:PDBe, RCSB
標識
代號 MLL; ALL-1; CXXC7; HRX; HTRX1; KMT2A; MLL/GAS7; MLL1A; TET1-MLL; TRX1; WDSTS
擴展標識 遺傳學159555 鼠基因96995 同源基因4338 ChEMBL: 1293299 GeneCards: MLL Gene
EC編號 2.1.1.43
RNA表達模式
更多表達數據
直系同源體
物種 人類 小鼠
Entrez 4297 214162
Ensembl ENSG00000118058 ENSMUSG00000002028
UniProt Q03164 P55200
mRNA序列 NM_001197104 NM_001081049
蛋白序列 NP_001184033 NP_001074518
基因位置 Chr 11:
118.31 – 118.4 Mb
Chr 9:
44.8 – 44.88 Mb
PubMed查詢 [1] [2]

MLL是一種組蛋白甲基轉移酶,被認為是影響基因轉錄的全局正向調控物。該蛋白屬於組蛋白修飾酶類家族,包含了轉活化結構域9aaTAD[2],且參與了對轉錄記憶的表觀遺傳學維持。

MLL基因若發生重排(即染色體結構改變造成遺傳物質的重新排列)則會導致嚴重的急性白血病,包括淋巴母細胞性及髓性[3]。該基因亦可能參與了精神分裂症GAD67表達下調的過程[4]

交互作用

現已顯示MLL這個基因與HDAC1[5]PPP1R15A[6]宿主細胞因子C1[7]MEN1[7] RBBP5,[7] ASH2L,[7]CREB結合蛋白[8][9]WDR5[7] CTBP1[5]PPIE.[10]之間有著相互作用

參考文獻

  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. 
  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. 
  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. 
  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. 
  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. 
  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. 
  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. 
  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. 
  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. 
  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. 

深入閱讀

  • 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. 

外部連結