Regulation of Cyclin G2 Degradation in Human Ovarian Cancer Cells

Epithelial ovarian cancer has the highest mortality rate among gynecological malignancies. Uncontrolled cell growth lies at the core of EOC. Normal cell cycle progression is governed by temporal expression of canonical cyclin molecules, which then bind to and activate CDKs. Cyclin G2, an unconventional cyclin, negatively regulates cell cycle and its levels are lowered in various types of cancer. Our lab has previously reported that cyclin G2 is an unstable protein, which is degraded by the UPP. Through a series of in vitro assays, we showed that cyclin G2 is a target of calpains proteolytic activity in a number of human ovarian cancer cells. Furthermore, we found that inhibition of EGFR in those cells led to protection of cyclin G2 from degradation. Finally, we demonstrated that EGF stimulation also resulted in degradation of cyclin G2. Considered together, these findings suggest that activation of EGFR and calpain promote cyclin G2 degradation.