Document Type

Article

Publication Date

3-1995

Publication Title

Proceedings of the National Academy of Sciences of the United States of America

Department

Geisel School of Medicine

Abstract

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.

Comments

This article has been retracted: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC56201/

Original Citation

Hajra A, Liu PP, Wang Q, et al. 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 [retracted in: Adelstein RS, Collins FS, Hajra A, Kelley CA, Liu PP, Speck NA, Stacy T, Wang Q. Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15523]. Proc Natl Acad Sci U S A. 1995;92(6):1926-1930. doi:10.1073/pnas.92.6.1926

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