Publication Date:
1998-09-04
Description:
Recruitment of the coactivator, CREB binding protein (CBP), by signal-regulated transcription factors, such as CREB [adenosine 3', 5'-monophosphate (cAMP) response element binding protein], is critical for stimulation of gene expression. The mouse pituitary cell line AtT20 was used to show that the CBP recruitment step (CREB phosphorylation on serine-133) can be uncoupled from CREB/CBP-activated transcription. CBP was found to contain a signal-regulated transcriptional activation domain that is controlled by nuclear calcium and calcium/calmodulin-dependent (CaM) protein kinase IV and by cAMP. Cytoplasmic calcium signals that stimulate the Ras mitogen-activated protein kinase signaling cascade or expression of the activated form of Ras provided the CBP recruitment signal but did not increase CBP activity and failed to activate CREB- and CBP-mediated transcription. These results identify CBP as a signal-regulated transcriptional coactivator and define a regulatory role for nuclear calcium and cAMP in CBP-dependent gene expression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chawla, S -- Hardingham, G E -- Quinn, D R -- Bading, H -- New York, N.Y. -- Science. 1998 Sep 4;281(5382):1505-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council, Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9727976" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
CREB-Binding Protein
;
Calcium/*metabolism
;
Calcium Channels/metabolism
;
Calcium-Calmodulin-Dependent Protein Kinase Type 2
;
Calcium-Calmodulin-Dependent Protein Kinase Type 4
;
Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors/*metabolism
;
Cell Line
;
Cell Nucleus/*metabolism
;
Cyclic AMP/metabolism
;
Cyclic AMP Response Element-Binding Protein/metabolism
;
Cytoplasm/metabolism
;
Genes, Reporter
;
Mice
;
Models, Genetic
;
Nuclear Proteins/*metabolism
;
Phosphorylation
;
Phosphoserine/metabolism
;
Recombinant Fusion Proteins/metabolism
;
Signal Transduction
;
Trans-Activators/*metabolism
;
Transcription, Genetic
;
*Transcriptional Activation
;
ras Proteins/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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