Differential pp40I kappa B-beta inhibition of DNA binding by rel proteins.
Open Access
- 1 March 1993
- journal article
- Published by Taylor & Francis in Molecular and Cellular Biology
- Vol. 13 (3), 1769-1778
- https://doi.org/10.1128/mcb.13.3.1769
Abstract
Regulation of gene expression by members of the NF-kappa B/rel transcription factor family is a central component of signal transduction pathways utilized by many cellular processes, including lymphocyte activation, embryonic development, and oncogenesis. The members of the NF-kappa B/rel transcription factor family are regulated by association with a family of inhibitor (I kappa B) proteins (I kappa B) proteins. To address the importance of the association between rel and I kappa B proteins for oncogenesis by rel proteins, we characterized rel-I kappa B interactions in chicken embryo fibroblasts (CEF) infected with retroviral vectors encoding the avian c-rel (p68c-rel), v-rel (p59v-rel), and I kappa B-beta (pp40I kappa B-beta) proteins. In these experiments, the p59v-rel:pp40I kappa B-beta ratio in coinfected CEF was nearly identical to the p59v-rel:pp40I kappa B-beta ratio in v-rel-transformed cells. The avian I kappa B-beta protein, pp40I kappa B-beta, was able to associate with both the nononcogenic p68c-rel and the oncogenic p59v-rel. Association of p68c-rel with pp40I kappa B-beta in coinfected CEF resulted in inhibition of the DNA-binding activity of p68c-rel. Anti-pp40I kappa B-beta serum was able to restore DNA binding to p68c-rel in the presence of high levels of pp40I kappa B-beta, indicating that pp40I kappa B-beta functions in a trans-acting manner to inhibit DNA binding by p68c-rel. In contrast, sequence-specific DNA binding by the oncogenic v-rel protein, p59v-rel, was not abolished by pp40I kappa B-beta in coinfected CEF. Anti-pp40I kappa B-beta serum did not immunoprecipitate the p59v-rel-DNA adduct or alter the electrophoretic mobility of the p59v-rel-DNA adduct, consistent with the idea that pp40I kappa B-beta and DNA are competitive inhibitors for the same or overlapping domains on rel proteins. Internal v-rel-derived sequences were identified that are responsible for loss of pp40I kappa B-beta-mediated inhibition of DNA binding by p59v-rel. Loss of pp40I kappa B-beta-mediated inhibition of DNA binding by recombinant v/c-rel proteins was not sufficient for oncogenic activation of c-rel. Instead, removal of C-terminal c-rel-derived sequences in addition to loss of pp40I kappa B-beta-mediated inhibition of DNA binding was required for oncogenic activation of c-rel. These results demonstrate the presence of an interaction between internal and C-terminal regions of the c-rel protein that is important for the ability of c-rel to regulate the proliferation of lymphoid cells.Keywords
This publication has 35 references indexed in Scilit:
- I-Rel: a novel rel-related protein that inhibits NF-kappa B transcriptional activity.Genes & Development, 1992
- Identification of a Naturally Occurring Transforming Variant of the p65 Subunit of NF-κBScience, 1992
- B cell lymphoma-associated chromosomal translocation involves candidate oncogene lyt-10, homologous to NF-κB p50Cell, 1991
- Rel-Associated pp40: an Inhibitor of the Rel Family of Transcription FactorsScience, 1991
- DNA binding and IκB inhibition of the cloned p65 subunit of NF-κB, a rel-related polypeptideCell, 1991
- The v-rel oncogene encodes a κB enhancer binding protein that inhibits NF-κB functionCell, 1990
- The DNA binding subunit of NF-κB is identical to factor KBF1 and homologous to the rel oncogene productCell, 1990
- Activation in vitro of NF-κB" by phosphorylation of its inhibitor IκB"Nature, 1990
- NF-κB: A pleiotropic mediator of inducible and tissue-specific gene controlCell, 1989
- Activation of DNA-binding activity in an apparently cytoplasmic precursor of the NF-κB transcription factorCell, 1988