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  • Original Paper
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Discreet mutations from c-Rel to v-Rel alter κB DNA recognition, IκBα binding, and dimerization: implications for v-Rel oncogenicity

Oncogene volume 23, pages 1229–1238 (2004)Cite this article

Abstract

The avian Rev-T retrovirus encodes the oncoprotein v-Rel, a member of the Rel/nuclear factor (NF)-κB transcription factor family. The aggressive oncogenic potential of v-Rel has arisen from multiple mutations within the coding sequence of the avian cellular protein c-Rel. In this study, using quantitative biochemical experiments, we have tested the role of a limited set of alterations between v-Rel and c-Rel located within the Rel homology region (RHR) of the family that might confer functional differences. Our results show that only a set of six mutations within the RHR of v-Rel are responsible for its ability to bind to a broad spectrum of κB-DNA that are normally regulated by distinct NF-κB dimers. We also observe that both v-Rel homodimer and p50/v-Rel heterodimer bind IκBα weakly compared to other cellular Rel/NF-κB dimers with transcription activation potential. We suggest that the ability of v-Rel homodimer to deregulate subunit-specific gene expression and its ability to evade IκB inhibition are crucial to its strong oncogenic potential.

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Acknowledgements

We thank Rashmi Talwer, Amanda Fusco, and Sebastien Vallee for their critical reading of this manuscript. This work was funded by grants from the California Cancer Research Program and the National Institute of Health. CP was funded by training grants from Cellular and Molecular Genetics and Growth and Oncogenesis at UCSD. DNA sequencing was performed by the Molecular Pathology Shared Resource, UCSD Cancer Center.

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  1. Department of Chemistry and Biochemistry, University of California, San Deigo, USA

    Christopher B Phelps & Gourisankar Ghosh

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  1. Christopher B Phelps
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  2. Gourisankar Ghosh
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Correspondence to Gourisankar Ghosh.

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Phelps, C., Ghosh, G. Discreet mutations from c-Rel to v-Rel alter κB DNA recognition, IκBα binding, and dimerization: implications for v-Rel oncogenicity. Oncogene 23, 1229–1238 (2004). https://doi.org/10.1038/sj.onc.1207242

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