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PMID: 8321203 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Functional and physical associations between NF-kappa B and C/EBP family members: a Rel domain-bZIP interaction.

Molecular and cellular biology ·Vol. 13 ·No. 7 ·1993-07-00 ·Pages 3964-74

Stein B, Cogswell PC, Baldwin AS

Abstract

NF-kappa B and C/EBP represent distinct families of transcription factors that target unique DNA enhancer elements. The heterodimeric NF-kappa B complex is composed of two subunits, a 50- and a 65-kDa protein. All members of the NF-kappa B family, including the product of the proto-oncogene c-rel, are characterized by their highly homologous approximately 300-amino-acid N-terminal region. This Rel homology domain mediates DNA binding, dimerization, and nuclear targeting of these proteins. C/EBP contains the bZIP region, which is characterized by two motifs in the C-terminal half of the protein: a basic region involved in DNA binding and a leucine zipper motif involved in dimerization. The C/EBP family consist of several related proteins, C/EBP alpha, C/EBP beta, C/EBP gamma, and C/EBP delta, that form homodimers and that form heterodimers with each other. We now demonstrated the unexpected cross-coupling of members of the NF-kappa B family three members of the C/EBP family. NF-kappa B p65, p50, and Rel functionally synergize with C/EBP alpha, C/EBP beta, and C/EBP delta. This cross-coupling results in the inhibition of promoters with kappa B enhancer motifs and in the synergistic stimulation of promoters with C/EBP binding sites. These studies demonstrate that NF-kappa B augments gene expression mediated by a multimerized c-fos serum response element in the presence of C/EBP. We show a direct physical association of the bZIP region of C/EBP with the Rel homology domain of NF-kappa B. The cross-coupling of NF-kappa B with C/EBP highlights a mechanism of gene regulation involving an interaction between distinct transcription factor families.

MeSH Terms
Amino Acid Sequence Animals Base Sequence Blotting, Western CCAAT-Enhancer-Binding Proteins Cell Line Cloning, Molecular DNA DNA-Binding Proteins/metabolism Haplorhini Humans Mice Molecular Sequence Data NF-kappa B/metabolism Nuclear Proteins/metabolism Promoter Regions, Genetic Proto-Oncogene Mas Transcription Factors/metabolism Tumor Cells, Cultured
Chemicals
CCAAT-Enhancer-Binding Proteins DNA-Binding Proteins MAS1 protein, human NF-kappa B Nuclear Proteins Proto-Oncogene Mas Transcription Factors DNA
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Stein B
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill 27599.
Cogswell P C
Baldwin A S
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.13.7.3964-3974.1993
Published
1993-07-00
Pages
3964-74
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC359940
Subset
IM
Grants
NCI NIH HHS · CA 52515 · United States
External Links
PubMed source DOI: 10.1128/mcb.13.7.3964-3974.1993 PMC Full Text View journal details
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