title: SCFs in the new millennium.
abstract: Substrate-specific degradation is a key feature of the ubiquitin proteasome system. Substrate specificity is typically directed by the E3 or ubiquitin ligase; such specificity can be conferred either by ligase modification or expression or conversely via modification of substrates that permit their recognition by a specific E3 ligase. The most well-known example of such complexes are the Cullin-RING ligases (CRLs). CRLs are composed of one of seven cullin-family scaffold proteins; the CRL serves as a scaffold that interacts directly with a RING-domain enzyme (Rbx1/2) through an extensive protein-protein interface within the globular C-terminal domain. At the N terminus, the cullin associates with an adaptor protein through cullin-repeat motifs. This adaptor, in turn, facilitates recruitment of a substrate-specifying factor that recruits the target to be ubiquitylated. The prototypical CRL is the cul1-containing complex, commonly referred to as the Skp1-Cul1-Fbox (SCF) ligase. SCF ligases contribute to the timely destruction of numerous substrates thereby ensuring normal cell growth. The importance of SCF function is highlighted by cancer-specific alterations in either the expression or the function of select F-box substrate-specific adaptors that results in neoplastic conversion. Herein, we discuss the current understanding of SCF function and contribution to cell biology.
authors.affiliation: 1] Leonard and Madlyn Abramson Family Cancer Research Institute, Philadelphia, PA, USA [2] Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: E K
authors.initials: EK
authors.lastname: Lee
authors.affiliation: 1] Leonard and Madlyn Abramson Family Cancer Research Institute, Philadelphia, PA, USA [2] Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Diehl
mesh_terms: D044842:Cullin Proteins / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D000075687:NEDD8 Protein; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism*; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism*; D013379:Substrate Specificity; D014452:Ubiquitins / Q000378:metabolism; D044844:beta-Transducin Repeat-Containing Proteins / Q000378:metabolism*
chemical_list: C100318:Cullin 1; D044842:Cullin Proteins; D000075687:NEDD8 Protein; C082860:NEDD8 protein, human; D044786:S-Phase Kinase-Associated Proteins; C097351:SKP1 protein, human; D014452:Ubiquitins; D044844:beta-Transducin Repeat-Containing Proteins; D044843:SKP Cullin F-Box Protein Ligases