Mapping of a serine-rich domain essential for the transcriptional, antiapoptotic, and transforming activities of the v-Rel oncoprotein

Mol Cell Biol. 1999 Jan;19(1):307-16. doi: 10.1128/MCB.19.1.307.

Abstract

The v-Rel oncoprotein belongs to the Rel/NF-kappaB family of transcription factors and induces aggressive lymphomas in chickens and transgenic mice. Current models for cell transformation by v-Rel invoke the combined activation of gene expression and the dominant inhibition of transcription mediated by its cellular homologs. Here, we mapped a serine-rich transactivation domain in the C terminus of v-Rel that is necessary for its biological activity. Specific serine-to-alanine substitutions within this region impaired the transcriptional activity of v-Rel, whereas a double mutant abolished its function. In contrast, substitutions with phosphomimetic aspartate residues led to a complete recovery of the transcriptional potential. The transforming activity of v-Rel mutants correlated with their ability to inhibit programmed cell death. The transforming and antiapoptotic activities of v-Rel were abolished by defined Ser-to-Ala mutations and restored by most Ser-to-Asp substitutions. However, one Ser-to-Asp mutant showed wild-type transactivation ability but failed to block apoptosis and to transform cells. These results show that the transactivation function of v-Rel is necessary but not sufficient for cell transformation, adding an important dimension to the transformation model. It is possible that defined protein-protein interactions are also required to block apoptosis and transform cells. Since v-Rel is an acutely oncogenic member of the Rel/NF-kappaB family, our data raise the possibility that phosphorylation of its serine-rich transactivation domain may regulate its unique biological activity.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis*
  • Aspartic Acid
  • Binding Sites
  • COS Cells
  • Cell Transformation, Neoplastic*
  • Chickens
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Mutagenesis
  • Oncogene Proteins v-rel
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-rel
  • Retroviridae Proteins, Oncogenic / genetics*
  • Retroviridae Proteins, Oncogenic / metabolism
  • Serine*
  • Transcription, Genetic*
  • Transcriptional Activation
  • Tumor Cells, Cultured

Substances

  • Oncogene Proteins v-rel
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-rel
  • Retroviridae Proteins, Oncogenic
  • Aspartic Acid
  • Serine