CREM GENE - USE OF ALTERNATIVE DNA-BINDING DOMAINS GENERATES MULTIPLE ANTAGONISTS OF CAMP-INDUCED TRANSCRIPTION
CREM GENE - USE OF ALTERNATIVE DNA-BINDING DOMAINS GENERATES MULTIPLE ANTAGONISTS OF CAMP-INDUCED TRANSCRIPTION
复制标题
DOI：
10.1016/0092-8674(91)90503-q
复制
发表时间：
1991-02-22
期刊：
影响因子：
64.5
通讯作者：
SASSONECORSI, P
中科院分区：
文献类型：
--
作者：
FOULKES, NS;BORRELLI, E;SASSONECORSI, P
我们从小鼠垂体 cDNA 文库中分离出一个基因，该基因编码与核因子 CREB 高度同源的蛋白质，CREB 是 cAMP 响应启动子元件 (CRE) 的激活剂。 我们证明，虽然 CREB 在多种细胞类型中一致表达，但该基因（称为 CREM）显示细胞特异性表达。 CREM 有一个非凡的组织，因为终止密码子的下游有第二个框架外的 DNA 结合域。 使用 PCR 和 RNAase 保护分析，我们鉴定了三种 mRNA 亚型，它们似乎是通过差异细胞特异性剪接获得的。 同种型的测序证明了两个 DNA 结合域的替代用途。 CREM 蛋白与 CREB 具有相同的 CRE 序列结合效率和特异性，但与 CREB 不同，CREM 充当 cAMP 诱导转录的下调因子。
We isolated a gene from a mouse pituitary cDNA library that encodes a protein highly homologous to nuclear factor CREB, an activator of cAMP-responsive promoter elements (CREs). We demonstrate that while CREB is expressed uniformly in several cell types, this gene, termed CREM, shows cell-specific expression. CREM has a remarkable organization, since downstream of the stop codon there is a second, out-of-frame DNA-binding domain. Using PCR and RNAase protection analysis, we have identified three mRNA isoforms that appear to be obtained by differential cell-specific splicing. Sequencing of the isoforms demonstrated alternative usage of the two DNA-binding domains. CREM proteins reveal the same efficiency and specificity of binding to CRE sequences as CREB, but in contrast to CREB, CREM acts as a down-regulator of cAMP-induced transcription.