CBP-independent activation of CREM and CREB by the LIM-only protein ACT
CBP-independent activation of CREM and CREB by the LIM-only protein ACT
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DOI：
10.1038/18237
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发表时间：
1999-03-11
期刊：
影响因子：
64.8
通讯作者：
Sassone-Corsi, P
中科院分区：
文献类型：
--
作者：
Fimia, GM;De Cesare, D;Sassone-Corsi, P
CREB和CREM的转录激活需要激活结构域内丝氨酸残基的磷酸化（CREB中的Ser 133; CREM中的Ser 117），其结果是与共激活因子CBP相互作用1，2。激活剂CREM在雄性生殖细胞中高度表达，并且是减数分裂后基因表达所需的（2 - 4）。利用双杂交筛选，我们已经分离出一个睾丸衍生的互补DNA编码的蛋白质，我们称之为ACT（激活剂的CREM在睾丸），一个LIM-only蛋白，专门与CREM，ACT协调表达CREM在组织和发育调控的方式。它强烈刺激酵母和哺乳动物细胞中的CREM转录活性，并含有内在激活功能。由于ACT绕过了经典的激活要求，即Ser 117的磷酸化和与CBP的相互作用，它代表了CREM和CREB转录激活的新途径。ACT可能定义了一个以前未发现的组织特异性共激活因子，其功能可能是特定的不同的细胞分化程序。
Transcriptional activation by CREB and CREM requires phosphorylation of a serine residue within the activation domain (Ser 133 in CREB; Ser 117 in CREM) which as a result interacts with the coactivator CBP1,2. The activator CREM is highly expressed in male germ cells and is required for post-meiotic gene expression(2-4). Using a two-hybrid screen, we have isolated a testis-derived complementary DNA encoding a protein that we term ACT (for activator of CREM in testis), a LIM-only protein which specifically associates with CREM, ACT is expressed coordinately with CREM in a tissue- and developmentally regulated manner. It strongly stimulates CREM transcriptional activity in yeast and mammalian cells and contains an intrinsic activation function. As ACT bypasses the classical requirements for activation, namely phosphorylation of Ser 117 and interaction with CBP, it represents a new route for transcriptional activation by CREM and CREB. ACT may define a previously undiscovered class of tissue-specific coactivators whose function could be specific for distinct cellular differentiation programmes.