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PMID: 2138707 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

mXBP/CRE-BP2 and c-Jun form a complex which binds to the cyclic AMP, but not to the 12-O-tetradecanoylphorbol-13-acetate, response element.

Molecular and cellular biology ·Vol. 10 ·No. 4 ·1990-04-00 ·Pages 1609-21

Ivashkiv LB, Liou HC, Kara CJ, Lamph WW, Verma IM, Glimcher LH

Abstract

Proto-oncogene products c-Fos and c-Jun form a complex which binds with high affinity to the 12-O-tetradecanoylphorbol-13-acetate (TPA) response DNA element and which stimulates transcription of phorbol ester- inducible genes. We have previously identified, by screening a lambda gt11 expression library, murine protein mXBP, which binds to a sequence which overlaps the 3' end of the murine class II major histocompatibility complex A alpha gene X box, a conserved transcription element found upstream of all class II genes. Here, we demonstrate that the target sequence for mXBP is a consensus cyclic AMP response element (CRE). mXBP is a member of the leucine zipper family of DNA-binding proteins and has significant homology to oncoproteins c-Fos and c-Jun. The inferred amino acid sequence of mXBP shows near identity to human CRE-BP1, except it does not contain an internal proline-rich domain. Immunoprecipitation and glutaraldehyde cross-linking studies show that mXBP/CRE-BP2 can form a complex with c-Jun. Complex formation is dependent on intact leucine zipper domains in both proteins. mXBP-c-Jun complexes can coexist with c-Fos-c-Jun complexes and can bind with high affinity to CRE, but not to TPA response DNA element, sequences. These results suggest that changes in the expression of mXBP/CRE-BP2, c-Fos, and c-Jun, which alter the ratio of mXBP-c-Jun to c-Fos-c-Jun complexes, would affect the relative expression of cyclic AMP and phorbol ester-responsive genes. This provides support for a combinatorial model of gene regulation, whereby protein-protein interactions which alter the DNA binding specificity of protein complexes can expand the flexibility of cellular transcriptional responses.

MeSH Terms
Activating Transcription Factor 2 Amino Acid Sequence Animals Base Sequence Cell Line Cyclic AMP Response Element-Binding Protein DNA, Neoplasm/genetics,metabolism DNA-Binding Proteins/genetics,metabolism Genes, MHC Class II Lymphoma Molecular Sequence Data Protein Biosynthesis Protein-Tyrosine Kinases/metabolism Proto-Oncogene Mas Proto-Oncogene Proteins c-jun Regulatory Sequences, Nucleic Acid Tetradecanoylphorbol Acetate/metabolism Trans-Activators Transcription Factors/metabolism Transcription, Genetic
Chemicals
Activating Transcription Factor 2 Atf2 protein, mouse Cyclic AMP Response Element-Binding Protein DNA, Neoplasm DNA-Binding Proteins MAS1 protein, human Proto-Oncogene Mas Proto-Oncogene Proteins c-jun Trans-Activators Transcription Factors Protein-Tyrosine Kinases Tetradecanoylphorbol Acetate
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Ivashkiv L B
Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts.
Liou H C
Kara C J
Lamph W W
Verma I M
Glimcher L H
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.10.4.1609-1621.1990
Published
1990-04-00
Pages
1609-21
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC362266
Subset
IM
Grants
PHS HHS · A121163 · United States
NIGMS NIH HHS · GM 36864 · United States
Databases
GENBANK
M31629
External Links
PubMed source DOI: 10.1128/mcb.10.4.1609-1621.1990 PMC Full Text View journal details
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