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PMID: 1620118 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The RxxRxRxxC motif conserved in all Rel/kappa B proteins is essential for the DNA-binding activity and redox regulation of the v-Rel oncoprotein.

Molecular and cellular biology ·Vol. 12 ·No. 7 ·1992-07-00 ·Pages 3094-106

Kumar S, Rabson AB, Gélinas C

Abstract

The v- and c-Rel oncoproteins bind to oligonucleotides containing kappa B motifs, form heterodimers with other members of the Rel family, and modulate expression of genes linked to kappa B motifs. Here, we report that the RxxRxRxxC motif conserved in all Rel/kappa B family proteins is absolutely required for v-Rel protein-DNA contact and its resulting transforming activity. We also demonstrate that serine substitution of the cysteine residue conserved within this motif enables v-Rel to escape redox control, thereby promoting overall DNA binding. These mutant proteins retained the ability to competitively inhibit kappa B-mediated transcriptional activation of the human immunodeficiency virus long terminal repeat but failed to efficiently transform chicken lymphoid cells both in vitro and in vivo. Our data indicate that reduction of the conserved cysteine residue in the RxxRxRxxC motif may be required for optimal DNA-protein interactions. These results provide direct biochemical evidence that the DNA-binding activity of v-Rel is subject to redox control and that the conserved cysteine residue in the RxxRxRxxC motif is critical for this regulation. These studies suggest that the DNA-binding, transcriptional, and biological activities of Rel family proteins may also be subject to redox control in vivo.

MeSH Terms
Base Sequence Binding Sites Consensus Sequence Cysteine DNA Mutational Analysis DNA-Binding Proteins/genetics Humans Molecular Sequence Data Multigene Family Mutagenesis, Site-Directed Oncogene Proteins v-rel Oncogenes/genetics Oxidation-Reduction Retroviridae Proteins, Oncogenic/genetics Serine Transcription, Genetic Transformation, Genetic
Chemicals
DNA-Binding Proteins Oncogene Proteins v-rel Retroviridae Proteins, Oncogenic Serine Cysteine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Kumar S
Center for Advanced Biotechnology and Medicine, Piscataway, New Jersey 08854-5638.
Rabson A B
Gélinas C
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.12.7.3094-3106.1992
Published
1992-07-00
Pages
3094-106
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC364524
Subset
IM
Grants
NCI NIH HHS · CA54999 · United States
NCI NIH HHS · CA55487 · United States
External Links
PubMed source DOI: 10.1128/mcb.12.7.3094-3106.1992 PMC Full Text View journal details
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