Biology:RUNX1T1
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Short description: Protein-coding gene in humans
 Generic protein structure example |
Protein CBFA2T1 is a protein that in humans is encoded by the RUNX1T1 gene.[1][2][3]
Function
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]
- CBFA2T3,[5][6]
- Calcitriol receptor[7]
- GFI1,[8]
- Nuclear receptor co-repressor 1,[9][10]
- Nuclear receptor co-repressor 2,[10][11]
- PRKAR2A,[12] and
- Zinc finger and BTB domain-containing protein 16.[13][14]
References
- ↑ "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. October 1992. doi:10.1182/blood.V80.7.1825.1825. PMID 1391946.
- ↑ "CBFA2T1, a gene rearranged in human leukemia, is a member of a multigene family". Genomics 52 (3): 332–341. Dec 1998. doi:10.1006/geno.1998.5429. PMID 9790752.
- ↑ 3.0 3.1 "Entrez Gene: RUNX1T1 runt-related transcription factor 1; translocated to, 1 (cyclin D-related)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=862.
- ↑ "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. October 2005. doi:10.1038/nature04209. PMID 16189514. Bibcode: 2005Natur.437.1173R.
- ↑ 5.0 5.1 "Interactions between the leukaemia-associated ETO homologues of nuclear repressor proteins". Eur. J. Haematol. 71 (6): 439–47. Dec 2003. doi:10.1046/j.0902-4441.2003.00166.x. PMID 14703694.
- ↑ 6.0 6.1 "The transcriptional corepressor MTG16a contains a novel nucleolar targeting sequence deranged in t (16; 21)-positive myeloid malignancies". Oncogene 21 (43): 6703–12. September 2002. doi:10.1038/sj.onc.1205882. PMID 12242670.
- ↑ "AML-associated translocation products block vitamin D(3)-induced differentiation by sequestering the vitamin D(3) receptor". Cancer Res. 62 (23): 7050–8. Dec 2002. PMID 12460926.
- ↑ "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. 89 (5): 1005–18. August 2003. doi:10.1002/jcb.10548. PMID 12874834.
- ↑ "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. 21 (19): 6470–83. October 2001. doi:10.1128/mcb.21.19.6470-6483.2001. PMID 11533236.
- ↑ 10.0 10.1 "Oligomerization of ETO is obligatory for corepressor interaction". Mol. Cell. Biol. 21 (1): 156–63. January 2001. doi:10.1128/MCB.21.1.156-163.2001. PMID 11113190.
- ↑ "The Flt3 internal tandem duplication mutant inhibits the function of transcriptional repressors by blocking interactions with SMRT". Blood 103 (12): 4650–8. June 2004. doi:10.1182/blood-2003-08-2759. PMID 14982881.
- ↑ "MTG8 proto-oncoprotein interacts with the regulatory subunit of type II cyclic AMP-dependent protein kinase in lymphocytes". Oncogene 20 (43): 6225–32. September 2001. doi:10.1038/sj.onc.1204794. PMID 11593431.
- ↑ "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. March 2000. doi:10.1128/mcb.20.6.2075-2086.2000. PMID 10688654.
- ↑ "AML-1/ETO fusion protein is a dominant negative inhibitor of transcriptional repression by the promyelocytic leukemia zinc finger protein". Blood 96 (12): 3939–47. Dec 2000. doi:10.1182/blood.V96.12.3939. PMID 11090081.
Further reading
- "Acute myeloid leukemia with t(8;21)/AML1/ETO: a distinct biological and clinical entity". Haematologica 87 (3): 306–19. 2002. PMID 11869944.
- "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. 1992. doi:10.1016/0165-4608(92)90384-K. PMID 1423235.
- "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. 1995. doi:10.1002/gcc.2870130105. PMID 7541640.
- "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. 1994. doi:10.1182/blood.V84.7.2115.2115. PMID 7919324.
- "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. 1994. PMID 8137293.
- "The t(8;21) translocation in acute myeloid leukemia results in production of an AML1-MTG8 fusion transcript". EMBO J. 12 (7): 2715–21. 1993. doi:10.1002/j.1460-2075.1993.tb05933.x. PMID 8334990.
- "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. 1993. doi:10.1182/blood.V82.4.1270.1270. PMID 8353289.
- "Cloning and gene mapping of the mouse homologue of the CBFA2T1 gene associated with human acute myeloid leukemia". Genomics 29 (3): 755–759. 1996. doi:10.1006/geno.1995.9941. PMID 8575770.
- "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. 1996. doi:10.1182/blood.V88.5.1813.1813. PMID 8781439.
- "Polymorphism in the 3' untranslated region of MTG8 is associated with obesity in Pima Indian males". Biochem. Biophys. Res. Commun. 246 (3): 624–626. 1998. doi:10.1006/bbrc.1998.8683. PMID 9618262. https://zenodo.org/record/1229490.
- "Subcellular localization of the oncoprotein MTG8 (CDR/ETO) in neural cells". Oncogene 16 (20): 2609–2615. 1998. doi:10.1038/sj.onc.1201824. PMID 9632137.
- "Structure and expression of the human MTG8/ETO gene". Gene 212 (1): 103–109. 1998. doi:10.1016/S0378-1119(98)00141-3. PMID 9661669.
- "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. 1999. doi:10.1111/j.1349-7006.1999.tb00666.x. PMID 10076566.
- "Structure and expression pattern of a human MTG8/ETO family gene, MTGR1". Gene 241 (2): 287–295. 2000. doi:10.1016/S0378-1119(99)00481-3. PMID 10675041.
- "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. 2000. doi:10.1128/MCB.20.6.2075-2086.2000. PMID 10688654.
- "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. 2000. doi:10.1073/pnas.97.13.7521. PMID 10861016. Bibcode: 2000PNAS...97.7521M.
- "Nuclear import and subnuclear localization of the proto-oncoprotein ETO (MTG8)". Oncogene 19 (32): 3584–3597. 2000. doi:10.1038/sj.onc.1203689. PMID 10951564.
- "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. 2000. doi:10.1083/jcb.150.5.939. PMID 10973986.
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