Chen Ke, Jiao Xuanmao, Ashton Anthony, Di Rocco Agnese, Pestell Timothy G, Sun Yunguang, Zhao Jun, Casimiro Mathew C, Li Zhiping, Lisanti Michael P, McCue Peter A, Shen Duanwen, Achilefu Samuel, Rui Hallgeir, Pestell Richard G
Department of Cancer Biology, Thomas Jefferson University, Philadelphia, PA, 19107, USA.
Pennsylvania Cancer and Regenerative Medicine Research Center, Baruch S. Blumberg Institute, Pennsylvania Biotechnology Center, Wynnewood, PA, 19096, USA.
Oncogenesis. 2020 Sep 18;9(9):83. doi: 10.1038/s41389-020-00266-y.
The essential G-cyclin, CCND1, is a collaborative nuclear oncogene that is frequently overexpressed in cancer. D-type cyclins bind and activate CDK4 and CDK6 thereby contributing to G-S cell-cycle progression. In addition to the nucleus, herein cyclin D1 was also located in the cytoplasmic membrane. In contrast with the nuclear-localized form of cyclin D1 (cyclin D1), the cytoplasmic membrane-localized form of cyclin D1 (cyclin D1) induced transwell migration and the velocity of cellular migration. The cyclin D1 was sufficient to induce G-S cell-cycle progression, cellular proliferation, and colony formation. The cyclin D1 was sufficient to induce phosphorylation of the serine threonine kinase Akt (Ser473) and augmented extranuclear localized 17β-estradiol dendrimer conjugate (EDC)-mediated phosphorylation of Akt (Ser473). These studies suggest distinct subcellular compartments of cell cycle proteins may convey distinct functions.
关键的G周期蛋白CCND1是一种协同核癌基因，在癌症中经常过度表达。D型周期蛋白结合并激活CDK4和CDK6，从而促进G-S期细胞周期进程。除细胞核外，本文中细胞周期蛋白D1也定位于细胞质膜。与细胞核定位形式的细胞周期蛋白D1（细胞周期蛋白D1）相比，细胞质膜定位形式的细胞周期蛋白D1（细胞周期蛋白D1）诱导了Transwell迁移和细胞迁移速度。细胞周期蛋白D1足以诱导G-S期细胞周期进程、细胞增殖和集落形成。细胞周期蛋白D1足以诱导丝氨酸苏氨酸激酶Akt（Ser473）的磷酸化，并增强核外定位的17β-雌二醇树枝状聚合物缀合物（EDC）介导的Akt（Ser473）磷酸化。这些研究表明，细胞周期蛋白的不同亚细胞区室可能具有不同的功能。
