Department of Biology, Stern College for Women of Yeshiva University, New York, NY, USA.
Cell Cycle. 2012 Sep 1;11(17):3159-65. doi: 10.4161/cc.21194. Epub 2012 Aug 16.
The 40S ribosomal S6 kinase 1 (S6K1) is a conserved serine/threonine protein kinase that belongs to the AGC family of protein kinases, which also includes Akt and many others. S6K1 is the principal kinase effector downstream of the mammalian target of rapamycin complex 1 (mTORC1). S6K1 is sensitive to a wide range of signaling inputs, including growth factors, amino acids, energy levels and hypoxia. S6K1 relays these signals to regulate a growing list of substrates and interacting proteins in control of oncogenic processes, such as cell growth and proliferation, cell survival and apoptosis and cell migration and invasion. Several lines of evidence suggest an important role for S6K1 in estrogen receptor (ER)-positive breast cancer. S6K1 directly phosphorylates and activates ERα. Furthermore, S6K1 expression is estrogenically regulated. Therefore, hyperactivation of mTORC1/S6K1 signaling may be closely related to ER-positive status in breast cancer and may be utilized as a marker for prognosis and a therapeutic target.
40S 核糖体 S6 激酶 1（S6K1）是一种保守的丝氨酸/苏氨酸蛋白激酶，属于蛋白激酶 AGC 家族，该家族还包括 Akt 和许多其他激酶。S6K1 是哺乳动物雷帕霉素靶蛋白复合物 1（mTORC1）下游的主要激酶效应物。S6K1 对多种信号输入敏感，包括生长因子、氨基酸、能量水平和缺氧。S6K1 将这些信号传递下去，以调节细胞生长和增殖、细胞存活和凋亡以及细胞迁移和侵袭等致癌过程中越来越多的底物和相互作用蛋白。有几条证据表明 S6K1 在雌激素受体（ER）阳性乳腺癌中发挥着重要作用。S6K1 直接磷酸化并激活 ERα。此外，S6K1 的表达受雌激素调控。因此，mTORC1/S6K1 信号的过度激活可能与乳腺癌的 ER 阳性状态密切相关，并可能被用作预后标志物和治疗靶点。
