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Beschreibung

Protein CBFA2T1 (UniProt: Q06455, also known as Cyclin-D-related protein, Eight twenty one protein, Protein ETO, Protein MTG8, Zinc finger MYND domain-containing protein 2) is encoded by the RUNX1T1 (also known as AML1T1, CBFA2T1, CDR, ETO, MTG8, ZMYND2) gene (Gene ID: 862) in human. In acute myeloid leukemias (AMLs) a recurring chromosomal translocation termed as t(8,21) is reported to generates the AML1 (8:21) ETO leukemia fusion protein that contains the DNA-binding domain of 1 transcription factor RUNX1 and almost all of ETO. It is shown that RUNX1 and the AML1 ETO fusion protein are co-expressed in t(8,21) AML cells and antagonize each other s gene-regulatory functions by co-occupying the binding sites of AML1 ETO activated genes. Both AML1-ETO and the AML1 protein are reported to recognize the same consensus DNA-binding motif (TGT/CGGT). AML1 ETO can either activate or repress transcription of different target genes. It can activate transcription of genes via recruitment of p300 and can repress transcription by competitively displacing RUNX1 and recruiting corepressors such as histone deacetylase 3 (HDAC3). Myeloid leukemia cells with the t(8,21) translocation, such as Kasumi-1 cells, display elevated levels of Bcl-2 that prolongs their life span and contribute to the development of t(8,21) leukemia. (Ref.: Guo, C., et al. (2020). J. Biol. Chem. 295(13) 4212 4223, Klampfer, L., et al. (1996). Proc Natl Acad Sci USA. 93(24), 14059-14064).