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PMID: 8423807 Published · ppublish English Journal Article

N-terminal DNA-binding domains contribute to differential DNA-binding specificities of NF-kappa B p50 and p65.

Molecular and cellular biology ·Vol. 13 ·No. 2 ·1993-02-00 ·Pages 852-60

Toledano MB, Ghosh D, Trinh F, Leonard WJ

Abstract

We previously reported that either oxidation or alkylation of NF-kappa B in vitro abrogates DNA binding. We used this phenomenon to help elucidate structural determinants of NF-kappa B binding. We now demonstrate that Cys-62 of NF-kappa B p50 mediates the redox effect and lies within an N-terminal region required for DNA binding but not for dimerization. Several point mutations in this region confer a transdominant negative binding phenotype to p50. The region is highly conserved in all Rel family proteins, and we have determined that it is also critical for DNA binding of NF-kappa B p65. Replacement of the N-terminal region of p65 with the corresponding region from p50 changes its DNA-binding specificity towards that of p50. These data suggest that the N-terminal regions of p50 and p65 are critical for DNA binding and help determine the DNA-binding specificities of p50 and p65. We have defined within the N-terminal region a sequence motif, R(F/G)(R/K)YXCE, which is present in Rel family proteins and also in zinc finger proteins capable of binding to kappa B sites. The potential significance of this finding is discussed.

MeSH Terms
Amino Acid Sequence Base Sequence Binding Sites Cloning, Molecular Cysteine/metabolism DNA/metabolism Humans Molecular Sequence Data Mutation NF-kappa B/chemistry,genetics,metabolism Oxidation-Reduction Sequence Homology, Amino Acid
Chemicals
NF-kappa B DNA Cysteine
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Toledano M B
Section on Pulmonary and Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892.
Ghosh D
Trinh F
Leonard W J
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.13.2.852-860.1993
Published
1993-02-00
Pages
852-60
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC358968
Subset
IM
External Links
PubMed source DOI: 10.1128/mcb.13.2.852-860.1993 PMC Full Text View journal details
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