- MLL (gene)
-
"HRX" redirects here. For the bank holding, see Hypo Real Estate.
Histone-lysine N-methyltransferase HRX is an enzyme that in humans is encoded by the MLL (ALL1) gene.[1]
MLL is a histone methyltransferase deemed a positive global regulator of gene transcription. This protein belongs to the group of histone-modifying enzymes comprising transactivation domain 9aaTAD[2] and is involved in the epigenetic maintenance of transcriptional memory.
Rearrangements of the MLL gene are associated with aggressive acute leukemias (ALL).[3] It also may participate in the process of GAD67 downregulation in schizophrenia.[4]
Contents
Interactions
MLL (gene) has been shown to interact with HDAC1,[5] PPP1R15A,[6] Host cell factor C1,[7] MEN1,[7] RBBP5,[7] ASH2L,[7] CREB binding protein,[8][9] WDR5,[7] CTBP1[5] and PPIE.[10]
References
- ^ Ziemin-van der Poel S (January 1992). "Identification of a gene, MLL, that spans the breakpoint in 11q23 translocations associated with human leukemias". Proc Natl Acad Sci U S A 88 (23): 10735–9. doi:10.1073/pnas.88.23.10735. PMC 53005. PMID 1720549. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=53005.
- ^ Piskacek S, Gregor M, Nemethova M, Grabner M, Kovarik P, Piskacek M (June 2007). "Nine-amino-acid transactivation domain: establishment and prediction utilities". Genomics 89 (6): 756–68. doi:10.1016/j.ygeno.2007.02.003. PMID 17467953.; Piskacek M (November 2009). "Common Transactivation Motif 9aaTAD recruits multiple general co-activators TAF9, MED15, CBP and p300". Nature Precedings: Prepublication research and preliminary findings. doi:10.1038/npre.2009.3488.2.; Piskacek M (November 2009). "9aaTADs mimic DNA to interact with a pseudo-DNA Binding Domain KIX of Med15 (Molecular Chameleons)". Nature Preceedings: Prepublication research and preliminary findings. doi:10.1038/npre.2009.3939.1.; Goto NK, Zor T, Martinez-Yamout M, Dyson HJ, Wright PE (November 2002). "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. 277 (45): 43168–74. doi:10.1074/jbc.M207660200. PMID 12205094.; Prasad R, Yano T, Sorio C, Nakamura T, Rallapalli R, Gu Y, Leshkowitz D, Croce CM, Canaani E (December 1995). "Domains with transcriptional regulatory activity within the ALL1 and AF4 proteins involved in acute leukemia". Proc. Natl. Acad. Sci. U.S.A. 92 (26): 12160–4. doi:10.1073/pnas.92.26.12160. PMC 40316. PMID 8618864. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=40316.; Ernst P, Wang J, Huang M, Goodman RH, Korsmeyer SJ (April 2001). "MLL and CREB Bind Cooperatively to the Nuclear Coactivator CREB-Binding Protein". Mol. Cell. Biol. 21 (7): 2249–58. doi:10.1128/MCB.21.7.2249-2258.2001. PMC 86859. PMID 11259575. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=86859.
- ^ Guenther MG, Jenner RG, Chevalier B, Nakamura T, Croce CM, Canaani E, Young RA (June 2005). "Global and Hox-specific roles for the MLL1 methyltransferase". Proc. Natl. Acad. Sci. U.S.A. 102 (24): 8603–8. doi:10.1073/pnas.0503072102. PMC 1150839. PMID 15941828. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1150839.
- ^ Huang HS, Matevossian A, Whittle C, Kim SY, Schumacher A, Baker SP, Akbarian S (October 2007). "Prefrontal dysfunction in schizophrenia involves mixed-lineage leukemia 1-regulated histone methylation at GABAergic gene promoters". J. Neurosci. 27 (42): 11254–62. doi:10.1523/JNEUROSCI.3272-07.2007. PMID 17942719.
- ^ a b Xia, Zhen-Biao; Anderson Melanie, Diaz Manuel O, Zeleznik-Le Nancy J (July 2003). "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) 100 (14): 8342–7. doi:10.1073/pnas.1436338100. ISSN 0027-8424. PMC 166231. PMID 12829790. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=166231.
- ^ Adler, H T; Chinery R, Wu D Y, Kussick S J, Payne J M, Fornace A J, Tkachuk D C (October 1999). "Leukemic HRX Fusion Proteins Inhibit GADD34-Induced Apoptosis and Associate with the GADD34 and hSNF5/INI1 Proteins". Mol. Cell. Biol. (UNITED STATES) 19 (10): 7050–60. ISSN 0270-7306. PMC 84700. PMID 10490642. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=84700.
- ^ a b c d e Yokoyama, Akihiko; Wang Zhong, Wysocka Joanna, Sanyal Mrinmoy, Aufiero Deborah J, Kitabayashi Issay, Herr Winship, Cleary Michael L (July 2004). "Leukemia Proto-Oncoprotein MLL Forms a SET1-Like Histone Methyltransferase Complex with Menin To Regulate Hox Gene Expression". Mol. Cell. Biol. (United States) 24 (13): 5639–49. doi:10.1128/MCB.24.13.5639-5649.2004. ISSN 0270-7306. PMC 480881. PMID 15199122. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=480881.
- ^ Goto, Natalie K; Zor Tsaffrir, Martinez-Yamout Maria, Dyson H Jane, Wright Peter E (November 2002). "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) 277 (45): 43168–74. doi:10.1074/jbc.M207660200. ISSN 0021-9258. PMID 12205094.
- ^ Ernst, P; Wang J, Huang M, Goodman R H, Korsmeyer S J (April 2001). "MLL and CREB Bind Cooperatively to the Nuclear Coactivator CREB-Binding Protein". Mol. Cell. Biol. (United States) 21 (7): 2249–58. doi:10.1128/MCB.21.7.2249-2258.2001. ISSN 0270-7306. PMC 86859. PMID 11259575. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=86859.
- ^ Fair, K; Anderson M, Bulanova E, Mi H, Tropschug M, Diaz M O (May 2001). "Protein Interactions of the MLL PHD Fingers Modulate MLL Target Gene Regulation in Human Cells". Mol. Cell. Biol. (United States) 21 (10): 3589–97. doi:10.1128/MCB.21.10.3589-3597.2001. ISSN 0270-7306. PMC 100280. PMID 11313484. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=100280.
Further reading
- Marschalek R, Nilson I, Löchner K et al. (1998). "The structure of the human ALL-1/MLL/HRX gene". Leuk. Lymphoma 27 (5–6): 417–28. doi:10.3109/10428199709058308. PMID 9477123.
- Eguchi M, Eguchi-Ishimae M, Greaves M (2004). "The role of the MLL gene in infant leukemia". Int. J. Hematol. 78 (5): 390–401. doi:10.1007/BF02983811. PMID 14704031.
- Daser A, Rabbitts TH (2004). "Extending the repertoire of the mixed-lineage leukemia gene MLL in leukemogenesis". Genes Dev. 18 (9): 965–74. doi:10.1101/gad.1195504. PMID 15132992.
- Li ZY, Liu DP, Liang CC (2005). "New insight into the molecular mechanisms of MLL-associated leukemia". Leukemia 19 (2): 183–90. doi:10.1038/sj.leu.2403602. PMID 15618964.
- Douet-Guilbert N, Morel F, Le Bris MJ et al. (2005). "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 46 (1): 143–6. doi:10.1080/104281904000010783. PMID 15621793.
External links
- MeSH MLL+protein,+human
- Gene MLL on the Atlas of Genetics and Oncology
PDB gallery 
2j2s: SOLUTION STRUCTURE OF THE NONMETHYL-CPG-BINDING CXXC DOMAIN OF THE LEUKAEMIA-ASSOCIATED MLL HISTONE METHYLTRANSFERASETranscription factors and intracellular receptors (1) Basic domains (1.1) Basic leucine zipper (bZIP)Activating transcription factor (AATF, 1, 2, 3, 4, 5, 6, 7) · AP-1 (c-Fos, FOSB, FOSL1, FOSL2, JDP2, c-Jun, JUNB, JUND) · BACH (1, 2) · BATF · BLZF1 · C/EBP (α, β, γ, δ, ε, ζ) · CREB (1, 3, L1) · CREM · DBP · DDIT3 · GABPA · HLF · MAF (B, F, G, K) · NFE (2, L1, L2, L3) · NFIL3 · NRL · NRF (1, 2, 3) · XBP1(1.2) Basic helix-loop-helix (bHLH)ATOH1 · AhR · AHRR · ARNT · ASCL1 · BHLHB2 · BMAL (ARNTL, ARNTL2) · CLOCK · EPAS1 · FIGLA · HAND (1, 2) · HES (5, 6) · HEY (1, 2, L) · HES1 · HIF (1A, 3A) · ID (1, 2, 3, 4) · LYL1 · MESP2 · MXD4 · MYCL1 · MYCN · Myogenic regulatory factors (MyoD, Myogenin, MYF5, MYF6) · Neurogenins (1, 2, 3) · NeuroD (1, 2) · NPAS (1, 2, 3) · OLIG (1, 2) · Pho4 · Scleraxis · SIM (1, 2) · TAL (1, 2) · Twist · USF1(1.3) bHLH-ZIP(1.4) NF-1(1.5) RF-X(1.6) Basic helix-span-helix (bHSH)(2) Zinc finger DNA-binding domains (2.1) Nuclear receptor (Cys4)subfamily 1 (Thyroid hormone (α, β), CAR, FXR, LXR (α, β), PPAR (α, β/δ, γ), PXR, RAR (α, β, γ), ROR (α, β, γ), Rev-ErbA (α, β), VDR)
subfamily 2 (COUP-TF (I, II), Ear-2, HNF4 (α, γ), PNR, RXR (α, β, γ), Testicular receptor (2, 4), TLX)
subfamily 3 (Steroid hormone (Androgen, Estrogen (α, β), Glucocorticoid, Mineralocorticoid, Progesterone), Estrogen related (α, β, γ))
subfamily 4 NUR (NGFIB, NOR1, NURR1) · subfamily 5 (LRH-1, SF1) · subfamily 6 (GCNF) · subfamily 0 (DAX1, SHP)(2.2) Other Cys4(2.3) Cys2His2General transcription factors (TFIIA, TFIIB, TFIID, TFIIE (1, 2), TFIIF (1, 2), TFIIH (1, 2, 4, 2I, 3A, 3C1, 3C2))
ATBF1 · BCL (6, 11A, 11B) · CTCF · E4F1 · EGR (1, 2, 3, 4) · ERV3 · GFI1 · GLI-Krüppel family (1, 2, 3, REST, S2, YY1) · HIC (1, 2) · HIVEP (1, 2, 3) · IKZF (1, 2, 3) · ILF (2, 3) · KLF (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 17) · MTF1 · MYT1 · OSR1 · PRDM9 · SALL (1, 2, 3, 4) · SP (1, 2, 4, 7, 8) · TSHZ3 · WT1 · Zbtb7 (7A, 7B) · ZBTB (16, 17, 20, 32, 33, 40) · zinc finger (3, 7, 9, 10, 19, 22, 24, 33B, 34, 35, 41, 43, 44, 51, 74, 143, 146, 148, 165, 202, 217, 219, 238, 239, 259, 267, 268, 281, 295, 300, 318, 330, 346, 350, 365, 366, 384, 423, 451, 452, 471, 593, 638, 644, 649, 655)(2.4) Cys6(2.5) Alternating composition(3) Helix-turn-helix domains (3.1) HomeodomainARX · CDX (1, 2) · CRX · CUTL1 · DBX (1, 2) · DLX (3, 4, 5) · EMX2 · EN (1, 2) · FHL (1, 2, 3) · HESX1 · HHEX · HLX · Homeobox (A1, A2, A3, A4, A5, A7, A9, A10, A11, A13, B1, B2, B3, B4, B5, B6, B7, B8, B9, B13, C4, C5, C6, C8, C9, C10, C11, C12, C13, D1, D3, D4, D8, D9, D10, D11, D12, D13) · HOPX · IRX (1, 2, 3, 4, 5, 6, MKX) · LMX (1A, 1B) · MEIS (1, 2) · MEOX2 · MNX1 · MSX (1, 2) · NANOG · NKX (2-1, 2-2, 2-3, 2-5, 3-1, 3-2, 6-1, 6-2) · NOBOX · PBX (1, 2, 3) · PHF (1, 3, 6, 8, 10, 16, 17, 20, 21A) · PHOX (2A, 2B) · PITX (1, 2, 3) · POU domain (PIT-1, BRN-3: A, B, C, Octamer transcription factor: 1, 2, 3/4, 6, 7, 11) · OTX (1, 2) · PDX1 · SATB2 · SHOX2 · VAX1 · ZEB (1, 2)(3.2) Paired box(3.3) Fork head / winged helix(3.4) Heat Shock Factors(3.5) Tryptophan clusters(3.6) TEA domain(4) β-Scaffold factors with minor groove contacts (4.1) Rel homology region(4.2) STAT(4.3) p53(4.4) MADS box(4.6) TATA binding proteins(4.7) High-mobility group(4.10) Cold-shock domainCSDA, YBX1(4.11) Runt(0) Other transcription factors (0.2) HMGI(Y)(0.3) Pocket domain(0.6) Miscellaneoussee also transcription factor/coregulator deficiencies
B bsyn: dna (repl, cycl, reco, repr) · tscr (fact, tcrg, nucl, rnat, rept, ptts) · tltn (risu, pttl, nexn) · dnab, rnab/runp · stru (domn, 1°, 2°, 3°, 4°)Categories:- Human proteins
- Genetics
- Epigenetics
- Proteins
- Transcription factors
- Genetics stubs
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