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Molecular and Cellular Biology, January 1999, p. 307-316, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Mapping of a Serine-Rich Domain Essential for the Transcriptional, Antiapoptotic, and Transforming Activities of the v-Rel Oncoprotein

Cailin Chen,1 François Agnès,1,dagger and Céline Gélinas1,2,3,*

Center for Advanced Biotechnology and Medicine,1 Department of Biochemistry,2 and Cancer Institute of New Jersey,3 University of Medicine and Dentistry of New Jersey---Robert Wood Johnson Medical School, Piscataway, New Jersey 08854-5638

Received 17 June 1998/Returned for modification 13 August 1998/Accepted 23 September 1998

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

* Corresponding author. Mailing address: CABM, 679 Hoes Ln., Piscataway, NJ 08854-5638. Phone: (732) 235-5035. Fax: (732) 235-5289. E-mail: gelinas{at}mbcl.rutgers.edu.

dagger Present address: Centre de Biologie du Développement (UMR 5547 CNRS/UPS), 31062 Toulouse Cedex, France.

Molecular and Cellular Biology, January 1999, p. 307-316, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Rayet, B., Fan, Y., Gelinas, C. (2003). Mutations in the v-Rel Transactivation Domain Indicate Altered Phosphorylation and Identify a Subset of NF-{kappa}B-Regulated Cell Death Inhibitors Important for v-Rel Transforming Activity. Mol. Cell. Biol. 23: 1520-1533 [Abstract] [Full Text]  
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