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Cyclic AMP-responsive DNA-binding protein: structure based on a cloned placental cDNA
J P Hoeffler1, T E Meyer, Y Yun
1Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Boston.
Science (New York, N.Y.)
|December 9, 1988
Summary
Researchers identified a cyclic AMP-responsive element-binding protein (CREB) that binds to DNA sequences regulating gene transcription. This CREB protein has structural similarities to other transcription factors involved in cellular processes.
Area of Science:
- Molecular Biology
- Genetics
- Cellular Biology
Background:
- Cyclic AMP (cAMP) acts as a crucial intracellular second messenger.
- cAMP regulates the transcription of numerous cellular genes.
- A specific DNA sequence, TGACGTCA (cAMP-responsive element, CRE), mediates this transcriptional regulation.
Purpose of the Study:
- To isolate and characterize proteins that bind to the CRE sequence.
- To identify the specific CRE-binding protein (CREB) involved in cAMP-mediated gene regulation.
Main Methods:
- Screening of a placental lambda gt11 expression library using a radioactive CRE probe.
- Isolation and characterization of a cDNA encoding the CRE-binding protein.
Main Results:
- A cDNA encoding a 326-amino acid protein with CRE-binding properties was isolated.
- The identified protein, CREB, possesses a basic region adjacent to a leucine zipper-like sequence, implicated in DNA binding and protein-protein interactions.
- CREB features an acidic N-terminal region, potentially serving as a transcriptional activation domain.
- The DNA-binding domain of CREB shows structural homology to domains in c-jun and yeast GCN4 transcription factors.
Conclusions:
- A novel CRE-binding protein (CREB) was identified and characterized.
- CREB plays a role in cAMP-mediated gene transcription.
- Structural features of CREB suggest conserved mechanisms for DNA binding and transcriptional regulation across different species and pathways.
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