Cyclin E in normal physiology and disease states

E-type cyclins, collectively called cyclin E, represent key components of the core cell cycle machinery. In mammalian cells, two E-type cyclins, E1 and E2, activate cyclin-dependent kinase 2 (CDK2) and drive cell cycle progression by phosphorylating several cellular proteins. Abnormally elevated activity of cyclin E-CDK2 has been documented in many human tumor types. Moreover, cyclin E overexpression mediates resistance of tumor cells to various therapeutic agents. Recent work has revealed that the role of cyclin E extends well beyond cell proliferation and tumorigenesis, and it may regulate a diverse array of physiological and pathological processes. In this review, we discuss these various cyclin E functions and the potential for therapeutic targeting of cyclin E and cyclin E-CDK2 kinase. Cyclin E, a cell cycle protein, has a variety of non-canonical, cell cycle-independent physiological roles, such as regulating liver function, neurophysiology, spermatogenesis, and stem cell maintenance.The diversity of the physiological functions of cyclin E is achieved through activation or inhibition of CDKs, and possibly also via kinase-independent mechanisms.Cyclin E is frequently overexpressed in cancer. Deregulated cyclin E expression causes uncontrolled proliferation, replication stress, and genome instability of cancer cells, and is responsible for resistance of tumor cells to various therapeutic compounds.Targeting cyclin E may represent an effective anticancer strategy.