Phosphorylated CREB binds specifically to the nuclear protein CBP
Abstract
Cyclic AMP-regulated gene expression frequently involves a DNA element known as the cAMP-regulated enhancer (CRE). Many transcription factors bind to this element, including the protein CREB, which is activated as a result of phosphorylation by protein kinase A. This modification stimulates interaction with one or more of the general transcription factors or, alternatively, allows recruitment of a co-activator. Here we report that CREB phosphorylated by protein kinase A binds specifically to a nuclear protein of M(r) 265K which we term CBP (for CREB-binding protein). Fusion of a heterologous DNA-binding domain to the amino terminus of CBP enables the chimaeric protein to function as a protein kinase A-regulated transcriptional activator. We propose that CBP may participate in cAMP-regulated gene expression by interacting with the activated phosphorylated form of CREB.
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- Authors
- Chrivia, J. C., Kwok, R. P. S., Lamb, N., Hagiwara, M., Montminy, M. R., & Goodman, R. H.
- Affiliations
- Oregon Health & Science University (US)
- Centre National de la Recherche Scientifique (FR)
- Salk Institute for Biological Studies (US)
- Venue
- Nature
- Published
- 1993-10
- Volume
- 365
- Issue
- 6449
- Pages
- 855-859
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2033529039
- Cited by
- 2,052
- References
- 17
- Citations by year
- 2026: 11 · 2025: 26 · 2024: 39 · 2023: 15 · 2022: 30 · 2021: 24 · 2020: 35 · 2019: 35 · 2018: 33 · 2017: 38 · 2016: 41 · 2015: 41 · 2014: 55 · 2013: 56 · 2012: 59
- FWCI
- 21.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- CREB, CREB-binding protein, CREB phosphorylation, protein kinase A, transcriptional coactivator, transcriptional activation, protein-protein interaction, chimeric transcription factors
- MeSH terms
- Cyclic AMP, Amino Acid Sequence, Animals, Base Sequence, Binding Sites, Cell Line, Cloning, Molecular, DNA, Gene Expression Regulation, Humans, Molecular Sequence Data, Nuclear Proteins, Phosphorylation, Protein Binding, Recombinant Fusion Proteins, Thyroid Gland, Transcription Factors, Trans-Activators, Cyclic AMP Response Element-Binding Protein, Cyclic AMP-Dependent Protein Kinases, Genes, Reporter, CREB-Binding Protein, Mice
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