SCF complex

Skp, Cullin, F-box containing complex (or SCF complex) is a multi-protein E3 ubiquitin ligase complex catalyzing the ubiquitination of proteins destined for proteasomal degradation. It has important roles in the ubiquitination of proteins involved in the cell cycle and also marks various other cellular proteins for destruction.

Core Components

SCF contains three core subunits, and a number of less critical components:

SCF and Cell Cycle Regulation

Progression through the cell cycle in eukaryotes is regulated through synthesis/degradation and phosphorylation/dephosphorylation of cell-cycle-regulating proteins. Two ubiquitin ligases are crucial in the cell cycle. The anaphase-promoting complex or cyclosome (APC/C) controls the metaphase–anaphase transition when bound to its substrate-specific activating subunit Cdc20: this complex ubiquitinylates the separase-inhibiting protein securin, paving the way for separase to break cohesin and thus separate the sister chromatids at the centromere. APC/C with another activating subunit, Cdh1, is active in G1 phase and controls levels of the mitosis-regulating B-type cyclins.

SCF controls the transitions between G1/S and G2/M phases. Two F-box-protein-bound SCF complexes (SCF-Skp2 and SCF-β-TrCP), are most well studied among over 70 F-box proteins identified in humans. SCF-Skp2 mainly ubiquitinates and degrades cyclin-dependent kinase inhibitors (CKIs) such as p27 and p21 as well as the G1-/S-specific cyclin E, in vivo and in vitro. Therefore, SCF-Skp2 promotes cell-cycle progression and cell growth. On the other hand, SCF-βTrCP promotes proteolysis of Emi1, an APC/C-Cdh1 inhibitor, and Wee1, a Cdk1 inhibitor, in early mitosis via phosphorylation at their degron (the amino acid motif DSGXXS, where X can be any amino acid) by kinases such as Polo-like kinase 1 (Plk1) and Cdk1–cyclin B. SCF-βTrCP and APC/C control each other to regulate timely progression through the cell cycle. Lists of substrates of SCF-Skp2 and -βTrCP are still growing.

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