The leukemic core binding factor beta-smooth muscle myosin heavy chain (CBF beta-SMMHC) chimeric protein requires both CBF beta and myosin heavy chain domains for transformation of NIH 3T3 cells.
AUTOR(ES)
Hajra, A
RESUMO
An inversion of chromosome 16 associated with the M4Eo subtype of acute myeloid leukemia produces a chimeric protein fusing the beta subunit of the transcription factor core binding factor (CBF beta) to the tail region of smooth muscle myosin heavy chain (SMMHC). We investigated the oncogenic properties of this CBF beta-SMMHC chimeric protein using a 3T3 transformation assay. NIH 3T3 cells expressing CBF beta-SMMHC acquired a transformed phenotype, as indicated by their ability to form foci, grow in soft agarose, and form tumors in nude mice. Cells expressing normal CBF beta or the SMMHC tail domain did not become transformed. Electrophoretic mobility-shift assays showed that extracts from cells transformed by CBF beta-SMMHC no longer formed the normal CBF/DNA complex but instead formed a much larger complex that did not migrate into the gel. Analysis of CBF beta-SMMHC deletion mutants demonstrated that the chimeric protein was transforming only if two domains were both present: (i) CBF beta sequences necessary for association with the CBF alpha subunit, and (ii) SMMHC sequences important for the formation of multimeric filaments. These results are direct evidence that CBF beta-SMMHC can function as an oncoprotein.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=42395Documentos Relacionados
- Overexpression of core-binding factor alpha (CBF alpha) reverses cellular transformation by the CBF beta-smooth muscle myosin heavy chain chimeric oncoprotein.
- Overexpression of core-binding factor alpha (CBF alpha) reverses cellular transformation by the CBF beta-smooth muscle myosin heavy chain chimeric oncoprotein.
- Core binding factor beta-smooth muscle myosin heavy chain chimeric protein involved in acute myeloid leukemia forms unusual nuclear rod-like structures in transformed NIH 3T3 cells.
- The Leukemic Protein Core Binding Factor β (CBFβ)–Smooth-Muscle Myosin Heavy Chain Sequesters CBFα2 into Cytoskeletal Filaments and Aggregates
- Multimerization via Its Myosin Domain Facilitates Nuclear Localization and Inhibition of Core Binding Factor (CBF) Activities by the CBFβ-Smooth Muscle Myosin Heavy Chain Myeloid Leukemia Oncoprotein