Skp1Cullin1Fbox

Skp1Cullin1Fbox refers to the core functional organization of the SCF (Skp1-Cullin-1-F-box) E3 ubiquitin ligase, a modular complex that tags substrates with ubiquitin to mark them for degradation by the proteasome. In the conventional SCF complex, Skp1 serves as an adaptor that links the F-box protein, which acts as the substrate receptor, to Cullin-1, which provides the scaffold. Although Skp1, Cullin-1, and an F-box protein form the essential core, active SCF complexes typically include a RING-box protein (Rbx1) and an E2 enzyme to catalyze ubiquitin transfer.

Composition and interactions: F-box proteins are a diverse family classified into groups such as FBXW, FBXL, and FBXO, each recognizing specific substrates through distinct motifs or phosphorylation-dependent degrons. The F-box motif binds Skp1, which in turn docks onto Cullin-1, creating a modular platform that can recruit a wide range of substrates via the attached F-box protein. Rbx1 at the opposite end brings the E2-ubiquitin conjugate into position for ubiquitination.

Mechanism and regulation: The SCF complex catalyzes the transfer of ubiquitin from the E2 enzyme to substrate lysines, often forming polyubiquitin chains that signal proteasomal degradation. Cullin-1 activity is regulated by neddylation and deneddylation, affecting complex assembly and turnover. Substrate ubiquitination is influenced by post-translational modifications and cellular context, enabling precise control of protein levels.

Biological significance: SCF complexes regulate numerous cellular processes, including cell cycle progression, signal transduction, and transcription. Dysregulation of SCF activity or F-box protein specificity is implicated in diseases such as cancer and developmental disorders. The Skp1–Cullin–F-box module represents a conserved and adaptable mechanism for targeted protein degradation.