CBP: A signal-regulated transcriptional coactivator controlled by nuclear calcium and CaM kinase IV

被引:372
作者
Chawla, S [1 ]
Hardingham, GE [1 ]
Quinn, DR [1 ]
Bading, H [1 ]
机构
[1] MRC, Mol Biol Lab, Cambridge CB2 2QH, England
关键词
D O I
10.1126/science.281.5382.1505
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页码:1505 / 1509
页数:5
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