SCFbetaTrCP

SCFbetaTrCP refers to a class of ubiquitin ligase complexes within the SCF (Skp1-Cullin-F-box) family, in which the F-box protein beta-transducin repeat-containing protein (β-TrCP) serves as the substrate receptor. The SCFβTrCP ligases direct the ubiquitination and subsequent proteasomal degradation of a subset of phosphorylated substrates, thereby regulating diverse cellular processes.

The complex is composed of the core SCF scaffold—Cullin-1, Skp1, and the RING finger protein Roc1/Rbx1—together with the F-box protein β-TrCP. In humans, there are two paralogs of the receptor, β-TrCP1 and β-TrCP2 (also known as FBXW1 and FBXW11 in some annotations), which can both assemble into SCF complexes. The choice of paralog can influence substrate selectivity and expression patterns.

β-TrCP recognizes phosphorylated degron motifs in target proteins, commonly a DSGxxS or similar phosphodegron. Substrates are phosphorylated by kinases such as CK1 and GSK3, enabling binding by the WD40 repeats of β-TrCP. Once bound, the SCFβTrCP complex catalyzes the polyubiquitination of the substrate, marking it for degradation by the 26S proteasome.

Key substrates include IκBα, regulating NF-κB signaling; β-catenin, influencing Wnt signaling; Emi1, Cdc25A, and Claspin, which link cell cycle progression and DNA replication checkpoints; and various transcription factors such as Snail. Through these targets, SCFβTrCP participates in inflammation, development, cell cycle control, and responses to cellular stress.

Dysregulation of SCFβTrCP activity has been linked to cancer and inflammatory diseases, reflecting its broad role in controlling protein stability and signal transduction.