The t(3;21) fusion product, AML1/Evi-1 blocks AML1-induced transactivation by recruiting CtBP
Copyright policy )The t(3;21) fusion product, AML1/Evi-1 blocks AML1-induced transactivation by recruiting CtBP
AML1/Evi-1 is a chimeric protein that is derived from t(3;21), found in blastic transformation of chronic myelogenous leukemia. It is composed of the N-terminal AML1 portion with the DNA-binding Runt domain and the C-terminal Evi-1 portion. It has been shown to dominantly repress AML1-induced transactivation. The mechanism for it has been mainly attributed to competition with AML1 for the DNA-binding and for the interaction with PEBP2beta (CBFbeta), a partner protein which heterodimerizes with AML1. It was recently found that Evi-1 interacts with C-terminal binding protein (CtBP) to repress TGFbeta-induced transactivation. Here, we demonstrate that AML1/Evi-1 interacts with CtBP in SKH1 cells, a leukemic cell line which endogenously overexpresses AML1/Evi-1 and that AML1/Evi-1 requires the interaction with CtBP to repress AML1-induced transactivation. The association with CtBP is also required when AML1/Evi-1 blocks myeloid differentiation of 32Dcl3 cells induced by granulocyte colony-stimulating factor. Taken together, it is suggested that one of the mechanisms for AML1/Evi-1-associated leukemogenesis should be an aberrant recruitment of a corepressor complex by the chimeric protein.
- Dokkyo University Japan
- University of Tokyo Japan
Binding Sites, Chromosomes, Human, Pair 21, Blotting, Western, Cell Differentiation, Blotting, Northern, Phosphoproteins, Histone Deacetylases, MDS1 and EVI1 Complex Locus Protein, Artificial Gene Fusion, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Alcohol Oxidoreductases, Leukemia, Myeloid, Cricetinae, Core Binding Factor Alpha 2 Subunit, Granulocyte Colony-Stimulating Factor, Animals, Humans, Chromosomes, Human, Pair 3, Granulocytes
Binding Sites, Chromosomes, Human, Pair 21, Blotting, Western, Cell Differentiation, Blotting, Northern, Phosphoproteins, Histone Deacetylases, MDS1 and EVI1 Complex Locus Protein, Artificial Gene Fusion, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Alcohol Oxidoreductases, Leukemia, Myeloid, Cricetinae, Core Binding Factor Alpha 2 Subunit, Granulocyte Colony-Stimulating Factor, Animals, Humans, Chromosomes, Human, Pair 3, Granulocytes
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