Abstract
The v-ski oncogene promotes cellular transformation and myogenic differentiation. In quail embryo fibroblasts the two properties are displayed simultaneously and terminal muscle differentiation occurs only among cells already transformed by v-ski. To understand how the two phenotypes are derived from a single gene, we have undertaken to identify functionally important regions in v-ski and to test whether these regions can promote one phenotype without the other. We have generated both random and targeted mutations in v-ski and evaluated the effects of these mutations on expression, intracellular location, transformation, and myogenesis. Among a total of 26 mutants analysed, we have not found complete separation of the myogenic and transforming properties. Mutations in the region of v-Ski encoded by exon 1 of c-ski frequently abolish both its transformation and muscle differentiation activities, whereas mutations outside of this region are always tolerated. When expressed in cells from a minigene containing only the exon 1 sequence, the protein displays the transforming and myogenic activities similar to v-Ski. These results argue that the amino acid sequence encoded by exon 1 contains the core functional domain of the oncoprotein. To determine whether this functional domain has a structural counterpart, we have fragmented the v-Ski protein by limited proteolysis and found a single proteolytically stable domain spanning the entire exon 1-encoded region. Physical studies of the polypeptide encoded by exon 1 confirms that it folds into a compact, globular protein. The finding that both the transforming and myogenic properties of v-Ski are inseparable by mutation and are contained in a single domain suggests that they are derived from the same function.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Zheng, G., Teumer, J., Colmenares, C. et al. Identification of a core functional and structural domain of the v-Ski oncoprotein responsible for both transformation and myogenesis. Oncogene 15, 459–471 (1997). https://doi.org/10.1038/sj.onc.1201205
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1201205
Keywords
This article is cited by
-
Transcriptional cofactors Ski and SnoN are major regulators of the TGF-β/Smad signaling pathway in health and disease
Signal Transduction and Targeted Therapy (2018)
-
Factors of transforming growth factor ? signalling are co-regulated in human hepatocellular carcinoma
Virchows Archiv (2004)
-
Repression of TGF-β signaling by the oncogenic protein SKI in human melanomas: consequences for proliferation, survival, and metastasis
Oncogene (2003)