Practice question

Ordered progression through interphase depends on timely degradation of regulatory proteins via ubiquitination. The SCF complex, meaning Skp1-Cullin-F-box, is a modular cullin-RING E3 ligase active from late G1 to early M. Core components include scaffold Cullin1, adaptor Skp1, RING finger Rbx1 and interchangeable F-box protein conferring substrate specificity. Canonical function involves CDK inhibitor p27 Kip1. When Cyclin E-CDK2 phosphorylates p27 at Thr187, phosphodegron is recognized by F-box protein Skp2 together with accessory Cks1, leading to Lys48-linked polyubiquitination and proteasomal destruction. Similar processing removes p21, p57, Sic1 in yeast and Cdc6, E2F1. Degradation eliminates CDK inhibition, allowing CDK2-Cyclin E and CDK2-Cyclin A activation for origin firing and S-phase progression. In contrast, APC/C recognizes D-box and KEN-box substrates in mitosis. SCF therefore links CDK-mediated phosphorylation to irreversible elimination, creating forward-driven cycle. Alterations in Skp2 and Fbw7 F-box proteins cause accumulation of cyclin E and Myc contributing to tumorigenesis and uncontrolled proliferation associated with poor prognosis. Additional feedback loops involving polo-like kinases, phosphatases and SCF-mediated degradation reinforce irreversibility and protect against premature progression that would compromise genome integrity and viability.