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PMID: 1534408 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Molecular cloning of human CREB-2: an ATF/CREB transcription factor that can negatively regulate transcription from the cAMP response element.

Karpinski BA, Morle GD, Huggenvik J, Uhler MD, Leiden JM

Abstract

The cAMP response element (CRE) is an octanucleotide motif (TGACGTCA) that mediates diverse transcriptional regulatory effects. In this report we describe the isolation and characterization of a full-length cDNA that encodes a CRE binding protein called CREB-2. Like other ATF/CREB transcription factors, the 351-amino acid CREB-2 protein contains a COOH-terminal leucine-zipper motif and an adjacent basic domain. CREB-2 mRNA is expressed ubiquitously in human tumor cell lines and mouse organs suggesting that it is involved in regulating transcription in a wide variety of cell types. Overexpression of CREB-2 resulted in a consistent and significant repression of CRE-dependent transcription in CV-1 cells. Deletional analyses localized the transcriptional repressor activity of CREB-2 to a 102-amino acid COOH-terminal region (amino acids 249-351) that contains the leucine-zipper and basic domains of the molecule. These results demonstrate that CRE-dependent transcription can be both positively and negatively regulated by structurally related members of the ATF/CREB family.

Related Genes
MeSH Terms
Amino Acid Sequence Base Sequence Cloning, Molecular Cyclic AMP Response Element-Binding Protein DNA/genetics DNA-Binding Proteins/genetics Enhancer Elements, Genetic Gene Expression Humans Leucine Zippers Molecular Sequence Data Protein Kinase C/metabolism Protein Kinases/metabolism RNA, Messenger/genetics Receptors, Antigen, T-Cell, alpha-beta/genetics Receptors, Cyclic AMP Regulatory Sequences, Nucleic Acid Repressor Proteins/genetics Transcription Factors/genetics
Chemicals
Cyclic AMP Response Element-Binding Protein DNA-Binding Proteins RNA, Messenger Receptors, Antigen, T-Cell, alpha-beta Receptors, Cyclic AMP Repressor Proteins Transcription Factors DNA Protein Kinases Protein Kinase C
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Karpinski B A
Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor 48109.
Morle G D
Huggenvik J
Uhler M D
Leiden J M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1992-06-01
Pages
4820-4
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC49179
Subset
IM
Grants
NIAID NIH HHS · AI29673 · United States
NIGMS NIH HHS · GM38788 · United States
Databases
GENBANK
M86842
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