Core binding factor β- Smooth muscle myosin heavy chain chimeric protein involved in acute myeloid leukemia forms unusual nuclear rod-like structures in transformed NIH 3T3 cells

Cisca Wijmenga, Paula E. Gregory, Amitav Hajra, Evelin Schröck, Thomas Ried, Roland Eils, P. Paul Liu, Francis S. Collins

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Patients with the M4Eo subtype of acute myeloid leukemia almost invariably are found to have an inversion of chromosome 16 in their leukemic cells, which results in a gene fusion between the transcription factor called core binding factor β (CBF β) on 16q and a smooth muscle myosin heavy chain (SMMHC) gene on 16p. Subcellular localizations of the wild-type CBFβ and the CBFβ-SMMHC fusion protein were determined by immunofluorescence of NIH 3T3 cells that overexpress wild-type or fusion protein. Normal CBFβ showed an unexpected perinuclear pattern consistent with primary localization in the Golgi complex. The CBFβ-SMMHC fusion protein had a very different pattern. Nuclear staining included rod-like crystalline structures as long as 11 μm. The heterodimeric partner of CBFβ, CBFα, formed part of this complex. Cytoplasmic staining included stress fibers that colocalized with actin, probably as a consequence of the myosin heavy chain component of the fusion protein. Deletion of different regions of the CBFβ portion of the fusion protein showed that binding to CBFα was not required for nuclear translocation. However, deletion of parts of the SMMHC domain of the fusion protein involved in myosin-mediated filament formation resulted in proteins that did not form rod-like structures. These observations confirm previous indirect evidence that the CBFβ-SMMHC fusion protein is capable of forming macromolecular nuclear aggregates and suggests possible models for the mechanism of leukemic transformation.

Original languageEnglish
Pages (from-to)1630-1635
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number4
DOIs
StatePublished - 20 Feb 1996

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