Cdc34

Cdc34 is an essential ubiquitin-conjugating enzyme (E2) in the budding yeast Saccharomyces cerevisiae. It participates in the ubiquitination of substrates that are targeted by the SCF (Skp1–Cul1–F-box protein) ubiquitin ligase complex, marking them for degradation by the proteasome and thereby regulating progression through the cell cycle. The degradation of key regulators, such as the cyclin-dependent kinase inhibitor Sic1, is a central feature of Cdc34’s role in enabling the G1 to S phase transition.

Mechanistically, Cdc34 forms a thioester-linked ubiquitin intermediate via its active-site cysteine and transfers ubiquitin to substrates under the direction of an E3 ligase. For efficient polyubiquitin chain formation, Cdc34 relies on an extended acidic C-terminal tail that influences chain elongation and interaction with the SCF complex. Cdc34 collaborates with various SCF complexes that contain different F-box proteins, allowing it to target multiple substrates for timely proteolysis during the cell cycle.

Cdc34 homologs and related enzymes are conserved across eukaryotes, reflecting a core role in ubiquitin-mediated proteolysis and cell cycle control. In yeast, the enzyme is frequently studied as a model for understanding how ubiquitination coordinates cyclin-dependent kinase activity and regulated degradation to drive cell cycle progression. Its function illustrates the broader importance of the ubiquitin-proteasome system in cellular regulation.