Fimia G M, De Cesare D, Sassone-Corsi P
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS-INSERM-ULP, Illkirch, Strasbourg, France.
Nature. 1999 Mar 11;398(6723):165-9. doi: 10.1038/18237.
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 CBP. The activator CREM is highly expressed in male germ cells and is required for post-meiotic gene expression. 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.
CREB和CREM的转录激活需要激活域内一个丝氨酸残基（CREB中的Ser 133；CREM中的Ser 117）发生磷酸化，磷酸化后的该残基会与共激活因子CBP相互作用。激活因子CREM在雄性生殖细胞中高度表达，是减数分裂后基因表达所必需的。通过双杂交筛选，我们分离出了一个睾丸来源的互补DNA，它编码一种我们称为ACT（睾丸中CREM的激活因子）的蛋白质，ACT是一种仅含LIM结构域的蛋白质，它能特异性地与CREM结合。ACT与CREM在组织和发育调控方面协同表达。它能在酵母和哺乳动物细胞中强烈刺激CREM的转录活性，并具有内在的激活功能。由于ACT绕过了激活的经典要求，即Ser 117的磷酸化以及与CBP的相互作用，它代表了CREM和CREB转录激活的一条新途径。ACT可能定义了一类以前未被发现的组织特异性共激活因子，其功能可能对不同的细胞分化程序具有特异性。
