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 17β-estradiol dendrimer conjugate (EDC)-mediated phosphorylation of Akt (Ser473). These studies suggest distinct subcellular compartments of cell cycle proteins may convey distinct functions.