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Journal of Virology, November 2008, p. 10792-10802, Vol. 82, No. 21
0022-538X/08/$08.00+0     doi:10.1128/JVI.00903-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

CAPER{alpha} Is a Novel Rel-TAD-Interacting Factor That Inhibits Lymphocyte Transformation by the Potent Rel/NF-{kappa}B Oncoprotein v-Rel{triangledown}

Jui Dutta,1,2,{dagger} Gaofeng Fan,1,2 and Céline Gélinas1,3*

Center for Advanced Biotechnology and Medicine,1 Graduate Program in Biochemistry and Molecular Biology,2 Department of Biochemistry, Robert Wood Johnson Medical School, Piscataway, New Jersey 088543

Received 30 April 2008/ Accepted 15 August 2008

The Rel/NF-{kappa}B transcription factors are constitutively activated in many human cancers. The Rel proteins in this family are implicated in leukemia/lymphomagenesis, but the mechanism is not completely understood. Previous studies showed that the transcription activation domains (TADs) of the viral oncoprotein v-Rel and its cellular Rel/NF-{kappa}B homologues c-Rel and RelA are key determinants of their different transforming activities in primary lymphocytes. Substitution of a Rel TAD for that of RelA conferred a strong transforming phenotype upon RelA, which otherwise failed to transform cells. To gain insights into protein interactions that influence cell transformation by the Rel TADs, we identified factors that interact with the TAD of v-Rel, the most oncogenic member of the Rel/NF-{kappa}B family. We report that the coactivator for transcription factors AP-1 and estrogen receptors, CAPER{alpha}, interacts with the v-Rel TAD and potently synergizes v-Rel-mediated transactivation. Importantly, coexpression of CAPER{alpha} markedly reduced and delayed v-Rel's transforming activity in primary lymphocytes, whereas a dominant-negative mutant enhanced the kinetics of v-Rel-mediated transformation. Furthermore, small interfering RNA-mediated knockdown of CAPER{alpha} in v-Rel-transformed lymphocytes significantly enhanced colony formation in soft agar. Since the potency of Rel-mediated transactivation is an important determinant of lymphocyte transformation, as is Rel's ability to induce transcriptional repression, these data suggest that CAPER{alpha}'s interaction with the Rel TAD could modulate Rel/NF-{kappa}B's transforming activity by facilitating expression or dampening repression of specific gene subsets important for oncogenesis. Overall, this study identifies CAPER{alpha} as a new transcriptional coregulator for v-Rel and reveals an important role in modulating Rel's oncogenic activity.

* Corresponding author. Mailing address: CABM, 679 Hoes Lane, Piscataway, NJ 08854. Phone: (732) 235-5035. Fax: (732) 235-4466. E-mail: gelinas{at}cabm.rutgers.edu

{triangledown} Published ahead of print on 27 August 2008.

{dagger} Present address: Dana Farber Cancer Institute, Dept. of Medical Oncology, Harvard Medical School, 44 Binney Street, Boston, MA 02115.

Journal of Virology, November 2008, p. 10792-10802, Vol. 82, No. 21
0022-538X/08/$08.00+0     doi:10.1128/JVI.00903-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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