CAPERα is a novel Rel-TAD-interacting factor that inhibits lymphocyte transformation by the potent Rel/NF-κB oncoprotein v-Rel

Jui Dutta, Gaofeng Fan, Celine Gelinas

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

The Rel/NF-κB 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-κB 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-κB family. We report that the coactivator for transcription factors AP-1 and estrogen receptors, CAPERα, interacts with the v-Rel TAD and potently synergizes v-Rel-mediated transactivation. Importantly, coexpression of CAPERα 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 CAPERα 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 CAPERα's interaction with the Rel TAD could modulate Rel/NF-κB's transforming activity by facilitating expression or dampening repression of specific gene subsets important for oncogenesis. Overall, this study identifies CAPERα as a new transcriptional coregulator for v-Rel and reveals an important role in modulating Rel's oncogenic activity.

Original languageEnglish (US)
Pages (from-to)10792-10802
Number of pages11
JournalJournal of virology
Volume82
Issue number21
DOIs
StatePublished - Nov 2008

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Fingerprint Dive into the research topics of 'CAPERα is a novel Rel-TAD-interacting factor that inhibits lymphocyte transformation by the potent Rel/NF-κB oncoprotein v-Rel'. Together they form a unique fingerprint.

Cite this