The membrane-associated form of cyclin D1 enhances cellular invasion

The essential G(1)-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(1)-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(NL)), the cytoplasmic membrane-localized form of cyclin D1 (cyclin D1(MEM)) induced transwell migration and the velocity of cellular migration. The cyclin D1(MEM)was sufficient to induce G(1)-S cell-cycle progression, cellular proliferation, and colony formation. The cyclin D1(MEM)was sufficient to induce phosphorylation of the serine threonine kinase Akt (Ser473) and augmented extranuclear localized 17 beta-estradiol dendrimer conjugate (EDC)-mediated phosphorylation of Akt (Ser473). These studies suggest distinct subcellular compartments of cell cycle proteins may convey distinct functions.