The proto-oncogene BCL-3 encodes an IκB protein

Lawrence D. Kerr, Colin S. Duckett, Penny Wamsley, Qiang Zhang, Paul Chiao, Gary Nabel, Timothy W. McKeithan, Patrick A. Baeuerle, Inder M. Verma

Research output: Contribution to journalArticlepeer-review

Abstract

The bcl-3 gene product, overexpressed in chronic lymphocytic leukemia (CLL) patients with the translocation t(14;19), is a member of the IκB family. The bcl-3 protein is able to inhibit the DNA binding and trans-activation of authentic NF-κB heterodimers p50-p65 and p49-p65, as well as p50 and p49 homodimers. The bcl-3 protein does not inhibit either the DNA-binding activity of the Rel protein or its ability to trans-activate genes linked to the κB site. A human 37-kD protein (IκBα), identified previously as a member of the IκB family, is also unable to inhibit DNA-binding activity of the Rel protein. However, unlike bcl-3, the 37-kD (IκBα) protein has no effect on the DNA-binding activity of p50 or p49 homodimers. Two dimensional phosphotryptic peptide maps of the human bcl-3 and the human 37-kD (IκBα) proteins reveal that the phosphopeptides from the 37-kD (IκBα) protein are nested within the bcl-3 protein. Furthermore, bcl-3 antisera immunoprecipitates an in vitro-radiolabeled 37-kD (IκBα) protein. Proteins of 56 and 38 kD can be identified in HeLa cells stimulated with PMA and immunoprecipitated with bcl-3 antisera. Comparison of tryptic peptide maps of the bcl-3 protein synthesized in vitro, and p56 and p38 from HeLa cells, shows that they are all structurally related. Removal of the amino-terminal sequences of the bcl-3 protein generates a protein that inhibits the DNA binding of the p50-p65 heterodimer but, like the 37-kD (IκBα) protein, is no longer able to inhibit the binding of the p50 and p49 homodimers with κB DNA. We propose that the bcl-3 and 37-kD (IκBα) proteins are related and are members of the IκB family.

Original languageEnglish (US)
Pages (from-to)2352-2363
Number of pages12
JournalGenes & development
Volume6
Issue number12
StatePublished - Dec 1992
Externally publishedYes

Keywords

  • c-Rel
  • DNA binding
  • NF-κB
  • trans-activation

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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