Related Experiment Videos
Activation of cAMP and mitogen responsive genes relies on a common nuclear factor
J Arias1, A S Alberts, P Brindle
1Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, California 92037.
Abstract:
A number of signalling pathways stimulate transcription of target genes through nuclear factors whose activities are primarily regulated by phosphorylation. Cyclic AMP regulates the expression of numerous genes, for example, through the protein kinase-A (PKA)-mediated phosphorylation of transcription factor CREB at Ser 133. Although phosphorylation may stimulate transcriptional activators by modulating their nuclear transport or DNA-binding affinity, CREB belongs to a class of proteins whose phosphorylation appears specifically to enhance their trans-activation potential. Recent work describing a phospho-CREB binding protein (CBP) which interacts specifically with the CREB trans-activation domain prompted us to examine whether CBP is necessary for cAMP regulated transcription. We report here that microinjection of an anti-CBP antiserum into fibroblasts can inhibit transcription from a cAMP responsive promoter. Surprisingly, CBP also cooperates with upstream activators such as c-Jun, which are involved in mitogen responsive transcription. We propose that CBP is recruited to the promoter through interaction with certain phosphorylated factors, and that CBP may thus play a critical role in the transmission of inductive signals from cell surface receptor to the transcriptional apparatus.
Insights
Cyclic AMP-regulated transcription relies on the coactivator CREB-binding protein (CBP). Microinjection of anti-CBP antiserum inhibits transcription, revealing CBP
Area of Science:
- Molecular Biology
- Cell Signaling
Background:
- Gene transcription is often regulated by signaling pathways that phosphorylate nuclear factors.
- Cyclic AMP (cAMP) signaling regulates gene expression via protein kinase-A (PKA) phosphorylation of CREB at Ser 133.
- Phosphorylation can enhance transcriptional activators, particularly CREB, by boosting trans-activation potential.
Purpose of the Study:
- To investigate the necessity of CREB-binding protein (CBP) in cAMP-regulated transcription.
- To determine if CBP is a crucial mediator in signal transduction pathways affecting gene expression.
Main Methods:
- Microinjection of anti-CBP antiserum into fibroblasts.
- Analysis of transcription from cAMP-responsive promoters.
- Investigation of CBP's interaction with other transcription factors like c-Jun.
Main Results:
- Microinjection of anti-CBP antiserum inhibited transcription from cAMP-responsive promoters.
- CBP was found to cooperate with upstream activators, including c-Jun, involved in mitogen-responsive transcription.
- Evidence suggests CBP is recruited to promoters via phosphorylated factors.
Conclusions:
- CBP is essential for cAMP-regulated transcription.
- CBP acts as a coactivator, bridging phosphorylated transcription factors to the transcriptional machinery.
- CBP plays a critical role in signal transmission from cell surface receptors to gene transcription.