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

Cailin Chen, François Agnès, Céline Gélinas

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

The v-Rel oncoprotein belongs to the Rel/NF-κB 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- κB family, our data raise the possibility that phosphorylation of its serine-rich transactivation domain may regulate its unique biological activity.

Original languageEnglish (US)
Pages (from-to)307-316
Number of pages10
JournalMolecular and cellular biology
Volume19
Issue number1
DOIs
StatePublished - Jan 1999

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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