MATURATION OF HUMAN CYCLIN-E REQUIRES THE FUNCTION OF EUKARYOTIC CHAPERONIN CCT

Cyclin E, a partner of the cyclin-dependent kinase Cdk2, has been impl icated in positive control of the G(1)/S phase transition. Whereas deg radation of cyclin E has been shown to be exquisitely regulated by ubi quitination and proteasomal action, little is known about posttranscri ptional aspects of its biogenesis, In a yeast-based screen designed to identify human proteins that interact with human cyclin E, we identif ied components of the eukaryotic cytosolic chaperonin CCT, We found th at the endogenous CCT complex in yeast was essential for the maturatio n of cyclin E in vivo. Under conditions of impaired CCT function, cycl in E failed to accumulate. Furthermore, newly translated cyclin E, bot h in vitro in reticulocyte lysate and in vi ro in human cells in cultu re, is efficiently bound and processed by the CCT. In vitro, in the pr esence of ATP, the bound protein is folded and released in order to be come associated with Cdk2. Thus, both the acquisition of the native st ate and turnover of cyclin E involve ATP-dependent processes mediated by large oligomeric assemblies.