Skp1-Cullin 1-F-box protein beta-transducin repeat-containing protein E3 ubiquitin ligase complex (SCF(beta-TRCP))

The Skp1-Cullin 1-F-box protein beta-transducin repeat-containing protein (SCFβTRCP) E3 ubiquitin ligase complex is a multi-protein machinery essential for the selective degradation of regulatory proteins via the ubiquitin-proteasome system [1]. It belongs to the Cullin-RING ligase (CRL) family and is composed of four core subunits: Cullin 1 (CUL1), S-phase kinase-associated protein 1 (SKP1), Ring-box protein 1 (RBX1), and the F-box protein β-TRCP (either β-TRCP1/FBXW1 or β-TRCP2/FBXW11), which acts as the substrate recognition component [2]. The complex specifically recognizes substrates containing a conserved DSG(X)2+S phosphodegron motif, such as IκBα, β-catenin, and CDC25A [3]. By regulating the levels of these proteins, SCFβTRCP controls critical cellular processes including the NF-κB and Wnt signaling pathways, cell cycle progression, and apoptosis [4]. In human diseases, its dysregulation is frequently observed in various cancers, where it can function as an oncoprotein by degrading tumor suppressors or as a tumor suppressor by degrading oncoproteins [5]. Therapeutic strategies targeting this complex include the development of small-molecule inhibitors to stabilize its substrates and the design of Proteolysis Targeting Chimeras (PROTACs) that hijack the complex to degrade specific neo-substrates [6].

Other names

SCF-beta-TrCPSCF(BTRC)FBXW1-containing SCF complexBTRC-CUL1-SKP1 complexSCF(FBXW11) complex

The complex functions as an E3 ubiquitin ligase that facilitates the polyubiquitination of specific phosphorylated substrates, marking them for degradation by the 26S proteasome [1, 2].