Cyclin E2, a novel G(1) cyclin that binds Cdk2 and is aberrantly expressedin human cancers

A novel cyclin gene was discovered by searching an expressed sequence tag d atabase with a cyclin box profile. The human cyclin E2 gene encodes a 404-a mino-acid protein that is most closely related to cyclin E. Cyclin E2 assoc iates with Cdk2 in a functional kinase complex that is inhibited by both p2 7(Kip1) and p21(Cip1). The catalytic activity associated with cyclin E2 com plexes is cell cycle regulated and peaks at the G(1)/S transition. Overexpr ession of cyclin E2 in mammalian cells accelerates G(1), demonstrating that cyclin E2 may be rate limiting for G(1) progression. Unlike cyclin E1, whi ch is expressed in most proliferating normal and tumor cells, cyclin E2 lev els were low to undetectable in nontransformed cells and increased signific antly in tumor-derived cells. The discovery of a novel second cyclin E fami ly member suggests that multiple unique cyclin E-CDK complexes regulate cel l cycle progression.