The essential G1-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 G1-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 D1NL), the cytoplasmic membrane-localized form of cyclin D1 (cyclin D1MEM) induced transwell migration and the velocity of cellular migration. The cyclin D1MEM was sufficient to induce G1-S cell-cycle progression, cellular proliferation, and colony formation. The cyclin D1MEM 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.
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; Shen, Duanwen; Achilefu, Samuel; Rui, Hallgeir; and Pestell, Richard G, "The membrane-associated form of cyclin D1 enhances cellular invasion" (2020). Department of Cancer Biology Faculty Papers. Paper 169.
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