SCFCdc4s

SCFCdc4s, or SCF_Cdc4s, denotes a class of Skp1–Cul1–Rbx1 (SCF) E3 ubiquitin ligase complexes that use Cdc4-family F-box proteins as substrate receptors. The term encompasses organisms and contexts in which multiple Cdc4-like F-box proteins partner with the SCF core to form distinct ligases with overlapping but non-identical substrate sets.

Composition and mechanism: The core SCF scaffold consists of Cul1, Skp1, and Rbx1, while the interchangeable F-box component from the Cdc4 family provides substrate specificity through its WD40-repeat domain. Substrates are typically proteins that bear a phosphorylated degron motif recognized by the Cdc4 WD40 surface; upon ubiquitination, they are directed to the 26S proteasome.

Biological role: SCF^Cdc4s participate in regulation of cell cycle transitions, development, and responses to cellular stress by controlling levels of key regulators. In organisms with multiple Cdc4-like receptors, each receptor can direct degradation of a subset of substrates, enabling nuanced control of cellular processes.

Evolution and diversity: The expansion of Cdc4-like F-box proteins across eukaryotes reflects diversification of ubiquitin ligase networks. The exact substrate repertoires and regulatory inputs of SCF^Cdc4s vary by species and tissue context.

See also: SCF complex; Cdc4; ubiquitin–proteasome system; phosphodegron.