cAMP/PKA signaling promotes AKT deactivation by reducing CIP2A expression, thereby facilitating decidualization
cAMP/PKA signaling promotes AKT deactivation by reducing CIP2A expression, thereby facilitating decidualization
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DOI：
10.1016/j.mce.2023.111946
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发表时间：
2023-05-04
影响因子：
4.1
通讯作者：
Du，Meirong
中科院分区：
文献类型：
--
作者：
Zhao，Weijie;Xu，Chunfang;Du，Meirong
cAMP信号传导是众所周知的是必不可少的蜕膜化，但细节并不完全清楚。在这里，我们表明，cAMP信号促进AKT失活子宫内膜间质细胞，这有利于他们的蜕膜化。发现AKT的失活是PP 2A（AKT的主要磷酸酶）的几种抑制剂的表达减少的结果，其中CIP 2A是最突出的。CIP 2A的减少是蜕膜化所必需的，因为持续的CIP 2A表达会损害染色质重塑和几种蜕膜化标志物（IGFBP 1、PRL、MAOA和IL-15）的表达。此外，CIP 2A启动子对cAMP信号的响应性的分析表明ETS家族是cAMP信号和CIP 2A减少之间的桥梁。我们的研究结果为cAMP信号在蜕膜化中的作用提供了新的见解，并可能有利于开发新的治疗方法，用于蜕膜化缺陷，AKT驱动的肿瘤和逆转，胰岛素抵抗。
cAMP signaling is widely known to be indispensable for decidualization, but the details are not fully understood. Here, we show that cAMP signaling promotes AKT deactivation in endometrial stromal cells, which favors their decidualization. The deactivation of AKT is found to be a consequence of the reduced expression of several inhibitors of PP2A, the major phosphatase of AKT, with CIP2A being the most prominent. CIP2A reduction is obligatory for decidualization, as persistent CIP2A expression impairs chromatin remodeling and the expression of several decidualization markers (IGFBP1, PRL, MAOA, and IL-15). Furthermore, analyses of the responsiveness of the CIP2A promoter to cAMP signaling suggest the ETS family to be a bridge between cAMP signaling and CIP2A reduction. Our results provide novel insights into the role of cAMP signaling in decidualization and might benefit the development of novel therapies for decidualization deficiency, AKT-driven tumors, and the reverse, insulin resistance.