Regulation of estrogen rapid signaling through arginine methylation by PRMT1
Regulation of estrogen rapid signaling through arginine methylation by PRMT1
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DOI：
10.1016/j.molcel.2008.05.025
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发表时间：
2008-07-25
期刊：
影响因子：
16
通讯作者：
Corbo, Laura
中科院分区：
文献类型：
--
作者：
Le Romancer, Muriel;Treilleux, Isabelle;Corbo, Laura
有证据表明，雌激素受体α（ER α）是雌激素信号快速转导到下游激酶级联的核心;然而，这种非基因组功能的机制尚未完全了解。在这里，我们报告了一个范例的ER α调节通过精氨酸甲基化的PRMT 1，瞬时甲基化精氨酸260内的ER α DNA结合域。这种甲基化事件是通过触发其与PI 3 K和Src的p85亚基的相互作用来介导受体的核内功能所必需的。此外，我们发现，粘着斑激酶（FAK），Src基板参与迁移过程中，也在这个复杂的招聘。我们的数据表明，ER α的甲基化是发生在正常和恶性上皮乳腺细胞的细胞质中的生理过程，并且ER α在乳腺癌的一个子集中是高甲基化的。
Evidence is emerging that estrogen receptor alpha (ER alpha) is central to the rapid transduction of estrogen signaling to the downstream kinase cascades; however, the mechanisms underlying this nongenomic function are not fully understood. Here we report a paradigm of ER alpha regulation through arginine methylation by PRMT1, which transiently methylates arginine 260 within the ERa DNA-binding domain. This methylation event is required for mediating the extranuclear function of the receptor by triggering its interaction with the p85 subunit of PI3K and Src. Furthermore, we find that the focal adhesion kinase (FAK), a Src substrate involved in the migration process, is also recruited in this complex. Our data indicate that the methylation of ER alpha is a physiological process occurring in the cytoplasm of normal and malignant epithelial breast cells and that ER alpha is hypermethylated in a subset of breast cancers.