Cdc53Cul1

Cdc53Cul1 refers to the Cullin-1–based scaffold at the core of SCF (Skp1–Cdc53/Cul1–F-box) ubiquitin ligase complexes. In Saccharomyces cerevisiae, Cdc53 is the yeast homolog of Cullin-1, while Cul1 is the reference vertebrate homolog. The SCF complex is a modular E3 ubiquitin ligase composed of the scaffold Cdc53/Cul1, the adaptor Skp1, an F-box protein that serves as the substrate receptor, and the RING-finger protein Rbx1. The complex collaborates with an E2 conjugating enzyme to transfer ubiquitin to chosen substrates, targeting them for proteasomal degradation.

Function and substrates of SCF complexes depend on the F-box protein present. Common roles include regulation of cell cycle transitions and progression, in part by degrading inhibitors or regulators such as CDK inhibitors, cyclins, and other cell cycle–associated factors. Substrate specificity is conferred by the F-box component (for example, different F-box proteins recognize distinct targets), while Cdc53/Cul1 provides the conserved scaffold that coordinates assembly and activity.

Regulation of Cdc53/Cul1 activity involves post-translational modification of the cullin scaffold, notably neddylation with the small ubiquitin-like modifier Rub1 (NEDD8). Neddylation enhances ligase activity, whereas deneddylation modulates it. The SCF complex is essential for proper ubiquitin-mediated proteolysis in many organisms, and its disruption leads to cell cycle defects and broad cellular consequences. Cdc53Cul1 thus represents the conserved core of a major ubiquitin ligase family driving targeted protein degradation.