core-binding factor [CBF]-alpha 2; runt-related transcription factor 1; acute myeloid leukemia 1 protein; polyomavirus enhancer binding protein 2 alpha B subunit; PEBP2-alpha B; SL3-3 enhancer factor 1 alpha B subunit;SL3/AKV core-binding factor alpha B subunit (RUNX1, AML1, CBFA2)
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Function
- DNA-binding protein which specifically interacts with a sequence belonging to the group of enhancer core motifs, TGT/cGGT
- CBF binds to the core site, 5'-PYGPYGGT-3', of a number of enhancers & promoters, including
- murine leukemia virus
- polyomavirus enhancer
- T-cell receptor enhancers
- osteocalcin
- osteopontin
- bone sialoprotein
- collagen-1 alpha-1
- LCK
- IL-3
- GM-CSF promoters
- CBF-alpha subunit binds DNA & appears to have a role in development of normal hematopoiesis
- essential for normal fetal liver hematopoiesis in mice[2]
- isoform AML-1L interferes with the transactivation activity of RUNX1
- acts synergistically with ELF4 to transactivate IL-3 promoter & with ELF2 to transactivate mouse BLK promoter
- inhibits MYST4-dependent transcriptional activation
- heterodimer with CBFB
- RUNX1 binds DNA as a monomer through the Runt domain
- DNA-binding is increased by heterodimerization
- isoform AML-1L can neither bind DNA nor heterodimerize
- interacts with TLE1 & THOC4
- interacts with ELF1, ELF2 & SPI1
- interacts via its Runt domain with the ELF4 N-terminal region
- interaction with ELF2 isoform 2 (NERF-1a) may act to repress RUNX1-mediated transactivation
- interacts with MYST3 & MYST4
- interacts with SUV39H1, leading to abrogate transactivating & DNA-binding properties of RUNX1
- phosphorylated in its C-terminus upon IL-6 treatment
- phosphorylation enhances interaction with MYST3
Structure
- proline/serine/threonine rich region at the C-terminus is necessary for transcriptional activation of target genes
- contains 1 Runt domain
Compartment
Alternative splicing
Expression
- expressed in all tissues examined except brain & heart
- highest levels in thymus, bone marrow & peripheral blood
Pathology
- chromosomal translocation t(8;21)(q22;q22) involving RUNX1 with RUNX1T1 is a cause acute myeloid leukemia-M2 (AML-M2)
- chromosomal translocation t(3;21)(q26;q22) involving RUNX1 with with EAP, MSD1 or EVI1 is a cause of therapy-related myelodysplastic syndrome
- chromosomal translocation t(3;21)(q26;q22) involving RUNX1 with EAP, MSD1 or EVI1 is a cause of chronic myelogenous leukemia (CML)
- chromosomal translocation t(12;21)(p13;q22) involving RUNX1 with TEL is found in childhood acute lymphoblastic leukemia (ALL); the translocation fuses the 3'-end of TEL to the alternate 5'-exon of AML-1H
- chromosomal translocation t(16;21)(q24;q22) involving RUNX1 with CBFA2T3 is found in therapy-related myeloid malignancies
- defects in RUNX1 are the cause of familial platelet disorder with associated myeloid malignancy (FPDMM)
Laboratory
- RUNX1 genotyping
- chromosomal translocation t(12;21)(p13;q22.3)(ETV6,RUNX1)
- chromosomal translocation t(3;21)(q26;q22.3)(MECOM,RUNX1)
- chromosomal translocation t(8;21)(q22;q22.3)(RUNX1T1,RUNX1)
More general terms
References
- ↑ Meyers et al, Identification of AML-1 and the (8;21) translocation protein (AML-1/ETO) as sequence-specific DNA-binding proteins: the runt homology domain is required for DNA binding and protein- protein interactions. Mol Cell Biol 13(10):6336 1993 PMID: https://www.ncbi.nlm.nih.gov/pubmed/8413232
- ↑ 2.0 2.1 Okuda et al. AML1, the target of multiple chromosomal translocations in in human leukemia, is essential for normal fetal liver hematopoiesis. Cell 84:321-30 1996 PMID: https://www.ncbi.nlm.nih.gov/pubmed/8565077
- ↑ Atlas of genetics & cytogenetics in oncology & haematology http://atlasgeneticsoncology.org/genes/AML1.html
- ↑ GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=RUNX1
- ↑ UniProt http://www.uniprot.org/uniprot/Q01196.html