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Runt-related transcription factor 1; translocated to, 1 (cyclin D-related)

PDB rendering based on 1wq6.
Available structures
1wq6, 2dj8, 2h7b
Identifiers
Symbols RUNX1T1; AML1T1; CBFA2T1; CDR; ETO; MGC2796; MTG8; MTG8b; ZMYND2
External IDs OMIM133435 MGI104793 HomoloGene3801 GeneCards: RUNX1T1 Gene
RNA expression pattern
PBB GE RUNX1T1 205529 s at tn.png
PBB GE RUNX1T1 205528 s at tn.png
PBB GE RUNX1T1 216831 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 862 12395
Ensembl ENSG00000079102 ENSMUSG00000006586
UniProt Q06455 Q61909
RefSeq (mRNA) NM_004349 XM_975417
RefSeq (protein) NP_004340 XP_980511
Location (UCSC) Chr 8:
93.04 - 93.18 Mb
Chr 4:
13.67 - 13.82 Mb
PubMed search [1] [2]

Protein CBFA2T1 is a protein that in humans is encoded by the RUNX1T1 gene.[1][2][3]

The protein encoded by this gene is a putative zinc finger transcription factor and oncoprotein. In acute myeloid leukemia, especially in the M2 subtype, the t(8;21)(q22;q22) translocation is one of the most frequent karyotypic abnormalities. The translocation produces a chimeric gene made up of the 5'-region of the RUNX1 gene fused to the 3'-region of this gene. The chimeric protein is thought to associate with the nuclear corepressor/histone deacetylase complex to block hematopoietic differentiation. Several transcript variants encoding multiple isoforms have been found for this gene.[3]

Interactions

RUNX1T1 has been shown to interact with CBFA2T2,[4][5][6] Zinc finger and BTB domain-containing protein 16,[7][8] Nuclear receptor co-repressor 1,[9][10] Nuclear receptor co-repressor 2,[11][10] CBFA2T3,[5][6] GFI1,[12] Calcitriol receptor[13] and PRKAR2A.[14]

References

  1. ^ Erickson P, Gao J, Chang KS, Look T, Whisenant E, Raimondi S, Lasher R, Trujillo J, Rowley J, Drabkin H (Oct 1992). "Identification of breakpoints in t(8;21) acute myelogenous leukemia and isolation of a fusion transcript, AML1/ETO, with similarity to Drosophila segmentation gene, runt". Blood 80 (7): 1825–31. PMID 1391946.  
  2. ^ Calabi F, Cilli V (Dec 1998). "CBFA2T1, a gene rearranged in human leukemia, is a member of a multigene family". Genomics 52 (3): 332–41. doi:10.1006/geno.1998.5429. PMID 9790752.  
  3. ^ a b "Entrez Gene: RUNX1T1 runt-related transcription factor 1; translocated to, 1 (cyclin D-related)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=862.  
  4. ^ Rual, Jean-François; Venkatesan Kavitha, Hao Tong, Hirozane-Kishikawa Tomoko, Dricot Amélie, Li Ning, Berriz Gabriel F, Gibbons Francis D, Dreze Matija, Ayivi-Guedehoussou Nono, Klitgord Niels, Simon Christophe, Boxem Mike, Milstein Stuart, Rosenberg Jennifer, Goldberg Debra S, Zhang Lan V, Wong Sharyl L, Franklin Giovanni, Li Siming, Albala Joanna S, Lim Janghoo, Fraughton Carlene, Llamosas Estelle, Cevik Sebiha, Bex Camille, Lamesch Philippe, Sikorski Robert S, Vandenhaute Jean, Zoghbi Huda Y, Smolyar Alex, Bosak Stephanie, Sequerra Reynaldo, Doucette-Stamm Lynn, Cusick Michael E, Hill David E, Roth Frederick P, Vidal Marc (Oct. 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature (England) 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.  
  5. ^ a b Lindberg, Sofia Rondin; Olsson André, Persson Ann-Maj, Olsson Inge (Dec. 2003). "Interactions between the leukaemia-associated ETO homologues of nuclear repressor proteins". Eur. J. Haematol. (Denmark) 71 (6): 439–47. ISSN 0902-4441. PMID 14703694.  
  6. ^ a b Hoogeveen, André T; Rossetti Stefano, Stoyanova Violeta, Schonkeren Joris, Fenaroli Angelia, Schiaffonati Luisa, van Unen Leontine, Sacchi Nicoletta (Sep. 2002). "The transcriptional corepressor MTG16a contains a novel nucleolar targeting sequence deranged in t (16; 21)-positive myeloid malignancies". Oncogene (England) 21 (43): 6703–12. doi:10.1038/sj.onc.1205882. ISSN 0950-9232. PMID 12242670.  
  7. ^ Melnick, A M; Westendorf J J, Polinger A, Carlile G W, Arai S, Ball H J, Lutterbach B, Hiebert S W, Licht J D (Mar. 2000). "The ETO protein disrupted in t(8;21)-associated acute myeloid leukemia is a corepressor for the promyelocytic leukemia zinc finger protein". Mol. Cell. Biol. (UNITED STATES) 20 (6): 2075–86. ISSN 0270-7306. PMID 10688654.  
  8. ^ Melnick, A; Carlile G W, McConnell M J, Polinger A, Hiebert S W, Licht J D (Dec. 2000). "AML-1/ETO fusion protein is a dominant negative inhibitor of transcriptional repression by the promyelocytic leukemia zinc finger protein". Blood (UNITED STATES) 96 (12): 3939–47. ISSN 0006-4971. PMID 11090081.  
  9. ^ Amann, J M; Nip J, Strom D K, Lutterbach B, Harada H, Lenny N, Downing J R, Meyers S, Hiebert S W (Oct. 2001). "ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with multiple histone deacetylases and binds mSin3A through its oligomerization domain". Mol. Cell. Biol. (United States) 21 (19): 6470–83. ISSN 0270-7306. PMID 11533236.  
  10. ^ a b Zhang, J; Hug B A, Huang E Y, Chen C W, Gelmetti V, Maccarana M, Minucci S, Pelicci P G, Lazar M A (Jan. 2001). "Oligomerization of ETO is obligatory for corepressor interaction". Mol. Cell. Biol. (UNITED STATES) 21 (1): 156–63. doi:10.1128/MCB.21.1.156-163.2001. ISSN 0270-7306. PMID 11113190.  
  11. ^ Takahashi, Shinichiro; McConnell Melanie J, Harigae Hideo, Kaku Mitsuo, Sasaki Takeshi, Melnick Ari M, Licht Jonathan D (Jun. 2004). "The Flt3 internal tandem duplication mutant inhibits the function of transcriptional repressors by blocking interactions with SMRT". Blood (United States) 103 (12): 4650–8. doi:10.1182/blood-2003-08-2759. ISSN 0006-4971. PMID 14982881.  
  12. ^ McGhee, Laura; Bryan Josh, Elliott Liza, Grimes H Leighton, Kazanjian Avedis, Davis J Nathan, Meyers Shari (Aug. 2003). "Gfi-1 attaches to the nuclear matrix, associates with ETO (MTG8) and histone deacetylase proteins, and represses transcription using a TSA-sensitive mechanism". J. Cell. Biochem. (United States) 89 (5): 1005–18. doi:10.1002/jcb.10548. ISSN 0730-2312. PMID 12874834.  
  13. ^ Puccetti, Elena; Obradovic Darja, Beissert Tim, Bianchini Andrea, Washburn Birgit, Chiaradonna Ferdinando, Boehrer Simone, Hoelzer Dieter, Ottmann Oliver Gerhard, Pelicci Pier Giuseppe, Nervi Clara, Ruthardt Martin (Dec. 2002). "AML-associated translocation products block vitamin D(3)-induced differentiation by sequestering the vitamin D(3) receptor". Cancer Res. (United States) 62 (23): 7050–8. ISSN 0008-5472. PMID 12460926.  
  14. ^ Fukuyama, T; Sueoka E, Sugio Y, Otsuka T, Niho Y, Akagi K, Kozu T (Sep. 2001). "MTG8 proto-oncoprotein interacts with the regulatory subunit of type II cyclic AMP-dependent protein kinase in lymphocytes". Oncogene (England) 20 (43): 6225–32. doi:10.1038/sj.onc.1204794. ISSN 0950-9232. PMID 11593431.  

Further reading

  • Ferrara F, Del Vecchio L (2002). "Acute myeloid leukemia with t(8;21)/AML1/ETO: a distinct biological and clinical entity.". Haematologica 87 (3): 306–19. PMID 11869944.  
  • Nisson PE, Watkins PC, Sacchi N (1992). "Transcriptionally active chimeric gene derived from the fusion of the AML1 gene and a novel gene on chromosome 8 in t(8;21) leukemic cells.". Cancer Genet. Cytogenet. 63 (2): 81–8. doi:10.1016/0165-4608(92)90384-K. PMID 1423235.  
  • Era T, Asou N, Kunisada T, et al. (1995). "Identification of two transcripts of AML1/ETO-fused gene in t(8;21) leukemic cells and expression of wild-type ETO gene in hematopoietic cells.". Genes Chromosomes Cancer 13 (1): 25–33. doi:10.1002/gcc.2870130105. PMID 7541640.  
  • Tighe JE, Calabi F (1994). "Alternative, out-of-frame runt/MTG8 transcripts are encoded by the derivative (8) chromosome in the t(8;21) of acute myeloid leukemia M2.". Blood 84 (7): 2115–21. PMID 7919324.  
  • Erickson PF, Robinson M, Owens G, Drabkin HA (1994). "The ETO portion of acute myeloid leukemia t(8;21) fusion transcript encodes a highly evolutionarily conserved, putative transcription factor.". Cancer Res. 54 (7): 1782–6. PMID 8137293.  
  • Miyoshi H, Kozu T, Shimizu K, et al. (1993). "The t(8;21) translocation in acute myeloid leukemia results in production of an AML1-MTG8 fusion transcript.". Embo J. 12 (7): 2715–21. PMID 8334990.  
  • Kozu T, Miyoshi H, Shimizu K, et al. (1993). "Junctions of the AML1/MTG8(ETO) fusion are constant in t(8;21) acute myeloid leukemia detected by reverse transcription polymerase chain reaction.". Blood 82 (4): 1270–6. PMID 8353289.  
  • Niwa-Kawakita M, Miyoshi H, Gotoh O, et al. (1996). "Cloning and gene mapping of the mouse homologue of the CBFA2T1 gene associated with human acute myeloid leukemia.". Genomics 29 (3): 755–9. doi:10.1006/geno.1995.9941. PMID 8575770.  
  • Erickson PF, Dessev G, Lasher RS, et al. (1996). "ETO and AML1 phosphoproteins are expressed in CD34+ hematopoietic progenitors: implications for t(8;21) leukemogenesis and monitoring residual disease.". Blood 88 (5): 1813–23. PMID 8781439.  
  • Wolford JK, Bogardus C, Prochazka M (1998). "Polymorphism in the 3' untranslated region of MTG8 is associated with obesity in Pima Indian males.". Biochem. Biophys. Res. Commun. 246 (3): 624–6. doi:10.1006/bbrc.1998.8683. PMID 9618262.  
  • Sacchi N, Tamanini F, Willemsen R, et al. (1998). "Subcellular localization of the oncoprotein MTG8 (CDR/ETO) in neural cells.". Oncogene 16 (20): 2609–15. doi:10.1038/sj.onc.1201824. PMID 9632137.  
  • Wolford JK, Prochazka M (1998). "Structure and expression of the human MTG8/ETO gene.". Gene 212 (1): 103–9. doi:10.1016/S0378-1119(98)00141-3. PMID 9661669.  
  • Komori A, Sueoka E, Fujiki H, et al. (1999). "Association of MTG8 (ETO/CDR), a leukemia-related protein, with serine/threonine protein kinases and heat shock protein HSP90 in human hematopoietic cell lines.". Jpn. J. Cancer Res. 90 (1): 60–8. PMID 10076566.  
  • Morohoshi F, Mitani S, Mitsuhashi N, et al. (2000). "Structure and expression pattern of a human MTG8/ETO family gene, MTGR1.". Gene 241 (2): 287–95. doi:10.1016/S0378-1119(99)00481-3. PMID 10675041.  
  • Melnick AM, Westendorf JJ, Polinger A, et al. (2000). "The ETO protein disrupted in t(8;21)-associated acute myeloid leukemia is a corepressor for the promyelocytic leukemia zinc finger protein.". Mol. Cell. Biol. 20 (6): 2075–86. doi:10.1128/MCB.20.6.2075-2086.2000. PMID 10688654.  
  • Miyamoto T, Weissman IL, Akashi K (2000). "AML1/ETO-expressing nonleukemic stem cells in acute myelogenous leukemia with 8;21 chromosomal translocation.". Proc. Natl. Acad. Sci. U.S.A. 97 (13): 7521–6. doi:10.1073/pnas.97.13.7521. PMID 10861016.  
  • Odaka Y, Mally A, Elliott LT, Meyers S (2000). "Nuclear import and subnuclear localization of the proto-oncoprotein ETO (MTG8).". Oncogene 19 (32): 3584–97. doi:10.1038/sj.onc.1203689. PMID 10951564.  
  • Wood JD, Nucifora FC, Duan K, et al. (2000). "Atrophin-1, the dentato-rubral and pallido-luysian atrophy gene product, interacts with ETO/MTG8 in the nuclear matrix and represses transcription.". J. Cell Biol. 150 (5): 939–48. doi:10.1083/jcb.150.5.939. PMID 10973986.  
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