Cdc53

Cdc53, short for cell division cycle 53, is a conserved cullin family protein in Saccharomyces cerevisiae that serves as the core scaffold of Cullin-RING ubiquitin ligases (CRLs), particularly the SCF-type ligases. As the structural backbone, Cdc53 enables the assembly of modular CRLs by partnering with Skp1, the RING finger protein Rbx1, and one of many F-box proteins that determine substrate specificity.

These CRL complexes function as E3 ubiquitin ligases that tag specific regulatory proteins with ubiquitin, marking them for proteasomal degradation. In budding yeast, SCF-Cdc53 complexes contribute to cell cycle progression by promoting the destruction of inhibitors of S-phase entry, such as Sic1, thereby allowing DNA replication to begin. Beyond Sic1, CRLs regulate a variety of cell cycle regulators and replication factors, helping to ensure proper timing and genome stability.

Cdc53 is essential for viability; loss of function disrupts multiple cell cycle processes and often leads to arrest or severe growth defects. The activity of CRLs containing Cdc53 is modulated by neddylation, a modification by the ubiquitin-like Rub1, which activates the ligase. Deneddylation or defects in Rub1 conjugation compromise CRL activity and cell-cycle regulation.

Conservation and context: Cdc53 is homologous to mammalian CUL1, reflecting a conserved architecture of SCF and other CRL complexes across eukaryotes. The underlying principle is the same: cullin scaffolds coordinate ubiquitination via Skp1, Rbx1, and F-box–containing substrate receptors to control diverse cellular processes, especially the cell cycle.

See also: Cullin-RING ubiquitin ligases; SCF complex; F-box proteins; Sic1; Skp1; Rbx1; CUL1.