ATF2 的磷酸化与 NFY 的相互作用诱导促性腺激素细胞中的 c-Jun。
Phosphorylation of ATF2 and interaction with NFY induces c-Jun in the gonadotrope.
机构信息
Department of Reproductive Medicine, Center for Reproductive Science and Medicine, University of California San Diego, La Jolla, CA 92093-0674, USA.
出版信息
Mol Cell Endocrinol. 2013 Jan 30;365(2):316-26. doi: 10.1016/j.mce.2012.11.012. Epub 2012 Nov 20.
Abstract
Induction of c-Jun and c-Fos, partners that comprise the AP1 transcription factor, is critical for GnRH regulation of FSHβ gene expression. The signaling pathways that are necessary for regulation of AP1 in the gonadotrope cell are not known. Here, we investigate the mechanism of c-Jun induction by GnRH, the sole regulator of c-Jun in the gonadotrope. We identify that GnRH phosphorylates ATF2 via p38 and JNK, the same pathways responsible for GnRH induction of c-Jun. Upon phosphorylation, ATF2 binds the CRE element within the c-Jun proximal promoter and interacts with NFY. Functional ATF2 is necessary for both GnRH induction of c-Jun and FSHβ. Taken together, these studies elucidate the specificity of c-Jun induction by GnRH in the gonadotrope by demonstrating GnRH activation of the p38 and JNK signaling pathways that lead to phosphorylation of ATF2, providing critical insight into GnRH regulation of its target gene, the gonadotropin subunit FSHβ.
摘要
诱导 c-Jun 和 c-Fos 的形成，它们构成了 AP1 转录因子，这对于 GnRH 调节 FSHβ 基因表达至关重要。但是，调控促性腺激素细胞中 AP1 的信号通路尚不清楚。在这里，我们研究了 GnRH 诱导 c-Jun 的机制，这是促性腺激素细胞中 c-Jun 的唯一调节剂。我们发现 GnRH 通过 p38 和 JNK 磷酸化 ATF2，这是 GnRH 诱导 c-Jun 的相同途径。磷酸化后，ATF2 结合 c-Jun 近端启动子中的 CRE 元件，并与 NFY 相互作用。功能性 ATF2 对于 GnRH 诱导 c-Jun 和 FSHβ 都是必需的。综上所述，这些研究通过证明 GnRH 激活 p38 和 JNK 信号通路导致 ATF2 磷酸化，阐明了 GnRH 在促性腺激素细胞中诱导 c-Jun 的特异性，为 GnRH 调节其靶基因促性腺激素亚单位 FSHβ 提供了重要的见解。
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