PROTEOLYSIS AND THE G(1)-S TRANSITION - THE SCF CONNECTION

Temporal control of ubiquitin-proteasome mediated protein degradation is critical for normal G(1) and S phase progression. Recent work has s hown that central to the temporal control mechanism is a relationship between newly identified E3 ubiquitin protein ligases, designated SCFs (Skp1-cullin-F-box protein ligase complexes), which confer substrate specificity on ubiquitination reactions and the activities of protein kinases that phosphorylate substrates destined for destruction at spec ific sites, thereby converting them into preferred targets for ubiquit in modification catalyzed by SCFs. The constituents of SCFs are member s of evolutionary conserved protein families. SCF-based ubiquitination pathways may play a key role in diverse biological processes, such as cell proliferation, differentiation and development.