Insulin-like growth factor-I stimulates c-fos and c-jun transcription in PC12 cells
Insulin-like growth factor-I stimulates c-fos and c-jun transcription in PC12 cells
复制标题
胰岛素样生长因子-I 刺激 PC12 细胞中的 c-fos 和 c-jun 转录
DOI：
10.1016/0303-7207(94)90116-3
复制
发表时间：
1994
影响因子：
4.1
通讯作者：
J. Loeffler
中科院分区：
文献类型：
--
作者：
D. Monnier;A. Boutillier;P. Giraud;R. Chiu;D. Aunis;P. Feltz;J. Zwiller;J. Loeffler
我们分析了胰岛素样生长因子-I(IGF-I)的作用，IGF-I是一种多肽生长因子，通过特定的膜受体发挥有丝分裂作用。本实验研究了胰岛素样生长因子-I在PC12细胞中的转录调控作用。用标记的AP1共识结合序列(tre：TGACTCA)进行凝胶迁移率改变分析表明，trIGF-I处理后特异性结合增加。基因转移研究表明，API结合的增加是有功能的，因为IGF-I刺激了报告基因的转录，该报告基因含有与氯霉素乙酰转移酶(CAT)报告基因相连的最小tre。为了进一步研究IGF-I提高API活性的分子机制，我们使用含有各自启动子或特定调控元件的报告基因分析了FC-fosandc-jun的转录调控。对c-jun启动子的缺失研究表明，IGF-I通过位于转录起始点之前的132个碱基对内的酸性作用元件(S)刺激c-jun转录，可能是类似API的元件TGACATCA。类似的研究表明，IGF-I对c-fos的刺激需要一个跨越二联体对称元件(DSE)和FOS AP1样序列(FAP)的调节序列。进一步使用与最小无反应启动子相关的特定元件的实验表明，DSE是IGF-I诱导Fos的主要靶点。
We analyzed the effects of insulin-like growth factor-I (IGF-I), a polypeptide growth factor which exerts mitogenic effects via specific membrane receptors. The control of IGF-I onc-fosandc-juntranscription was studied in PC12 cells. Gel mobility shift assays with a labeled AP1 consensus binding sequence (TRE: TGACTCA) showed an increase in specific binding upon trIGF-I treatment. Gene transfer studies revealed that the increase in API binding is functional since IGF-I stimulates transcription from a reporter gene containing the minimal TRE linked to the chloramphenicol acetyl transferase (CAT) reporter gene. To further characterize the molecular mechanism by which IGF-I increases API activity, we analysed the transcription regulation ofc-fosandc-junusing reporter genes containing the respective promoters or specific regulatory elements. Deletion studies with thec-junpromoter, showed that IGF-I stimulatesc-juntranscription via acisacting element(s) localized within the 132 base pairs prior to the transcription start site; possibly the API like element TGACATCA. Similar studies revealed thatc-fosstimulation by IGF-I requires the presence of a regulatory sequence spanning the dyad symmetry element (DSE) and the fos AP1-like sequence (FAP). Further experiments using specific elements linked to the minimal unresponsivec-fospromoter, showed that the DSE is the main target forc-fosinduction by IGF-I.
影响因子：
56.9
作者：
SHENG, M;THOMPSON, MA;GREENBERG, ME
通讯作者：
GREENBERG, ME