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Runx1t1

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Title: Runx1t1  
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Subject: Acute myeloblastic leukemia with maturation, CBFA2T2, GFI1, CBFA2T3, Zinc finger and BTB domain-containing protein 16
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Runx1t1

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

PDB rendering based on 1wq6.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols  ; AML1T1; CBFA2T1; CDR; ETO; MTG8; ZMYND2
External IDs GeneCards:
RNA expression pattern
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

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,[10][11] 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 (October 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.  
  2. ^ Calabi F, Cilli V (Dec 1998). "CBFA2T1, a gene rearranged in human leukemia, is a member of a multigene family". Genomics 52 (3): 332–341.  
  3. ^ a b "Entrez Gene: RUNX1T1 runt-related transcription factor 1; translocated to, 1 (cyclin D-related)". 
  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 (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network".  
  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): 439–447.  
  6. ^ a b Hoogeveen, André T; Rossetti Stefano; Stoyanova Violeta; Schonkeren Joris; Fenaroli Angelia; Schiaffonati Luisa; van Unen Leontine; Sacchi Nicoletta (September 2002). "The transcriptional corepressor MTG16a contains a novel nucleolar targeting sequence deranged in t (16; 21)-positive myeloid malignancies". Oncogene (England) 21 (43): 6703–6712.  
  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 (March 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): 2075–2086.  
  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.  
  9. ^ Amann, J M; Nip J; Strom D K; Lutterbach B; Harada H; Lenny N; Downing J R; Meyers S; Hiebert S W (October 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): 6470–6483.  
  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 (January 2001). "Oligomerization of ETO is obligatory for corepressor interaction". Mol. Cell. Biol. (UNITED STATES) 21 (1): 156–163.  
  11. ^ Takahashi, Shinichiro; McConnell Melanie J; Harigae Hideo; Kaku Mitsuo; Sasaki Takeshi; Melnick Ari M; Licht Jonathan D (June 2004). "The Flt3 internal tandem duplication mutant inhibits the function of transcriptional repressors by blocking interactions with SMRT". Blood (United States) 103 (12): 4650–4658.  
  12. ^ McGhee, Laura; Bryan Josh; Elliott Liza; Grimes H Leighton; Kazanjian Avedis; Davis J Nathan; Meyers Shari (August 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): 1005–1018.  
  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.  
  14. ^ Fukuyama, T; Sueoka E; Sugio Y; Otsuka T; Niho Y; Akagi K; Kozu T (September 2001). "MTG8 proto-oncoprotein interacts with the regulatory subunit of type II cyclic AMP-dependent protein kinase in lymphocytes". Oncogene (England) 20 (43): 6225–6232.  

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.  
  • 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): 81–88.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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): 755–759.  
  • 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.  
  • 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): 624–626.  
  • Sacchi N, Tamanini F, Willemsen R et al. (1998). "Subcellular localization of the oncoprotein MTG8 (CDR/ETO) in neural cells". Oncogene 16 (20): 2609–2615.  
  • Wolford JK, Prochazka M (1998). "Structure and expression of the human MTG8/ETO gene". Gene 212 (1): 103–109.  
  • 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.  
  • Morohoshi F, Mitani S, Mitsuhashi N et al. (2000). "Structure and expression pattern of a human MTG8/ETO family gene, MTGR1". Gene 241 (2): 287–295.  
  • 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): 2075–2086.  
  • 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): 7521–7526.  
  • Odaka Y, Mally A, Elliott LT, Meyers S (2000). "Nuclear import and subnuclear localization of the proto-oncoprotein ETO (MTG8)". Oncogene 19 (32): 3584–3597.  
  • 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): 939–948.  


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