Discreet mutations from c-Rel to v-Rel alter kappaB DNA recognition, IkappaBalpha binding, and dimerization: implications for v-Rel oncogenicity

Oncogene. 2004 Feb 12;23(6):1229-38. doi: 10.1038/sj.onc.1207242.

Abstract

The avian Rev-T retrovirus encodes the oncoprotein v-Rel, a member of the Rel/nuclear factor (NF)-kappaB 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 kappaB-DNA that are normally regulated by distinct NF-kappaB dimers. We also observe that both v-Rel homodimer and p50/v-Rel heterodimer bind IkappaBalpha weakly compared to other cellular Rel/NF-kappaB 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 IkappaB inhibition are crucial to its strong oncogenic potential.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Chickens
  • Cloning, Molecular
  • DNA / chemistry
  • DNA / genetics*
  • DNA / metabolism
  • DNA Primers
  • Dimerization
  • Escherichia coli / genetics
  • Humans
  • I-kappa B Proteins / metabolism*
  • Mutagenesis, Site-Directed
  • Mutation*
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Oncogene Proteins v-rel / genetics*
  • Proto-Oncogene Proteins c-rel / genetics*
  • Recombinant Proteins / metabolism
  • Sequence Homology, Nucleic Acid

Substances

  • DNA Primers
  • I-kappa B Proteins
  • NF-kappa B
  • NFKBIA protein, human
  • Oncogene Proteins v-rel
  • Proto-Oncogene Proteins c-rel
  • Recombinant Proteins
  • NF-KappaB Inhibitor alpha
  • DNA