CBP: A Signal-Regulated Transcriptional Coactivator Controlled by Nuclear Calcium and CaM Kinase IV

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 C...

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Veröffentlicht in:Science (American Association for the Advancement of Science) 1998-09, Vol.281 (5382), p.1505-1509
Hauptverfasser: Chawla, Sangeeta, Hardingham, Giles E., Quinn, David R., Bading, Hilmar
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Sprache:eng
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Zusammenfassung: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.281.5382.1505