9de2

Structural highlights

Disease

MTG16_HUMAN Acute megakaryoblastic leukemia in children without Down syndrome. A chromosomal aberration involving CBFA2T3 is found in therapy-related myeloid malignancies. Translocation t(16;21)(q24;q22) that forms a RUNX1-CBFA2T3 fusion protein.^{[1] [2] [3]}

Function

MTG16_HUMAN Transcriptional corepressor which facilitates transcriptional repression via its association with DNA-binding transcription factors and recruitment of other corepressors and histone-modifying enzymes (PubMed:12559562, PubMed:15203199). Can repress the expression of MMP7 in a ZBTB33-dependent manner (PubMed:23251453). Reduces the protein levels and stability of the transcriptinal regulator HIF1A; interacts with EGLN1 and promotes the HIF1A prolyl hydroxylation-dependent ubiquitination and proteasomal degradation pathway (PubMed:25974097). Contributes to inhibition of glycolysis and stimulation of mitochondrial respiration by down-regulating the expression of glycolytic genes including PFKFB3, PFKFB4, PDK1, PFKP, LDHA and HK1 which are direct targets of HIF1A (PubMed:23840896, PubMed:25974097). Regulates the proliferation and the differentiation of erythroid progenitors by repressing the expression of TAL1 target genes (By similarity). Plays a role in granulocyte differentiation (PubMed:15231665).[UniProtKB:O54972]^{[4] [5] [6] [7] [8] [9] [10] [11]} Isoform 2 functions as an A-kinase-anchoring protein (PubMed:11823486).^[12]

References

1. ↑ Salomon-Nguyen F, Busson-Le Coniat M, Lafage Pochitaloff M, Mozziconacci J, Berger R, Bernard OA. AML1-MTG16 fusion gene in therapy-related acute leukemia with t(16;21)(q24;q22): two new cases. Leukemia. 2000 Sep;14(9):1704-5. PMID:10995019 doi:10.1038/sj.leu.2401885
2. ↑ La Starza R, Sambani C, Crescenzi B, Matteucci C, Martelli MF, Mecucci C. AML1/MTG16 fusion gene from a t(16;21)(q24;q22) translocation in treatment-induced leukemia after breast cancer. Haematologica. 2001 Feb;86(2):212-3 PMID:11224496
3. ↑ Gamou T, Kitamura E, Hosoda F, Shimizu K, Shinohara K, Hayashi Y, Nagase T, Yokoyama Y, Ohki M. The partner gene of AML1 in t(16;21) myeloid malignancies is a novel member of the MTG8(ETO) family. Blood. 1998 Jun 1;91(11):4028-37 PMID:9596646
4. ↑ Kochetkova M, McKenzie OL, Bais AJ, Martin JM, Secker GA, Seshadri R, Powell JA, Hinze SJ, Gardner AE, Spendlove HE, O'Callaghan NJ, Cleton-Jansen AM, Cornelisse C, Whitmore SA, Crawford J, Kremmidiotis G, Sutherland GR, Callen DF. CBFA2T3 (MTG16) is a putative breast tumor suppressor gene from the breast cancer loss of heterozygosity region at 16q24.3. Cancer Res. 2002 Aug 15;62(16):4599-604 PMID:12183414
5. ↑ Ibañez V, Sharma A, Buonamici S, Verma A, Kalakonda S, Wang J, Kadkol S, Saunthararajah Y. AML1-ETO decreases ETO-2 (MTG16) interactions with nuclear receptor corepressor, an effect that impairs granulocyte differentiation. Cancer Res. 2004 Jul 1;64(13):4547-54. PMID:15231665 doi:10.1158/0008-5472.CAN-03-3689
6. ↑ Kumar R, Manning J, Spendlove HE, Kremmidiotis G, McKirdy R, Lee J, Millband DN, Cheney KM, Stampfer MR, Dwivedi PP, Morris HA, Callen DF. ZNF652, a novel zinc finger protein, interacts with the putative breast tumor suppressor CBFA2T3 to repress transcription. Mol Cancer Res. 2006 Sep;4(9):655-65. PMID:16966434 doi:10.1158/1541-7786.MCR-05-0249
7. ↑ Barrett CW, Smith JJ, Lu LC, Markham N, Stengel KR, Short SP, Zhang B, Hunt AA, Fingleton BM, Carnahan RH, Engel ME, Chen X, Beauchamp RD, Wilson KT, Hiebert SW, Reynolds AB, Williams CS. Kaiso directs the transcriptional corepressor MTG16 to the Kaiso binding site in target promoters. PLoS One. 2012;7(12):e51205. PMID:23251453 doi:10.1371/journal.pone.0051205
8. ↑ Kumar P, Sharoyko VV, Spégel P, Gullberg U, Mulder H, Olsson I, Ajore R. The transcriptional co-repressor myeloid translocation gene 16 inhibits glycolysis and stimulates mitochondrial respiration. PLoS One. 2013 Jul 1;8(7):e68502. PMID:23840896 doi:10.1371/journal.pone.0068502
9. ↑ Kumar P, Gullberg U, Olsson I, Ajore R. Myeloid translocation gene-16 co-repressor promotes degradation of hypoxia-inducible factor 1. PLoS One. 2015 May 14;10(5):e0123725. PMID:25974097 doi:10.1371/journal.pone.0123725
10. ↑ Davis JN, McGhee L, Meyers S. The ETO (MTG8) gene family. Gene. 2003 Jan 16;303:1-10. PMID:12559562 doi:10.1016/s0378-1119(02)01172-1
11. ↑ Rossetti S, Hoogeveen AT, Sacchi N. The MTG proteins: chromatin repression players with a passion for networking. Genomics. 2004 Jul;84(1):1-9. PMID:15203199 doi:10.1016/j.ygeno.2004.02.011
12. ↑ Schillace RV, Andrews SF, Liberty GA, Davey MP, Carr DW. Identification and characterization of myeloid translocation gene 16b as a novel a kinase anchoring protein in T lymphocytes. J Immunol. 2002 Feb 15;168(4):1590-9. PMID:11823486 doi:10.4049/jimmunol.168.4.1590