CBP: A signal-regulated transcriptional coactivator controlled by nuclear calcium and CaM kinase IV
CBP: A signal-regulated transcriptional coactivator controlled by nuclear calcium and CaM kinase IV
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DOI：
10.1126/science.281.5382.1505
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发表时间：
1998-09-04
期刊：
影响因子：
56.9
通讯作者：
Bading, H
中科院分区：
文献类型：
--
作者：
Chawla, S;Hardingham, GE;Bading, H
通过信号调节转录因子，如CREB [腺苷3 '，5'-单磷酸（cAMP）反应元件结合蛋白]募集共激活因子CREB结合蛋白（CBP）。是刺激基因表达的关键。小鼠垂体细胞系AtT 20用于显示CBP募集步骤（CREB在丝氨酸-133上的磷酸化）可以与CREB/CBP激活的转录解偶联。CBP被发现含有一个信号调节的转录激活结构域，该结构域由核钙和钙/钙调蛋白依赖性（CaM）蛋白激酶IV以及cAMP控制。刺激Ras促分裂原活化蛋白激酶信号级联或Ras活化形式表达的细胞质钙信号提供CBP募集信号，但不增加CBP活性，并且未能激活CREB和CBP介导的转录。这些结果确定CBP作为一个信号调节的转录辅激活因子，并定义了CBP依赖的基因表达的核钙和cAMP的调节作用。
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.