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 as well as having a role in the marking various other cellular proteins for destruction.

SCF contains three core subunits, and a number of less critical components:
 * F-box protein - (Such as cdc4) Contributes to the specificity of SCF by aggregating to target proteins independently of the complex and then binding to the Skp1 component, thus allowing the protein to be brought into proximity with the functional E2 protein. The F-box is also essential in regulating SCF activity during the course of the cell-cycle. SCF levels are thought to remain constant throughout the cell-cycle. Instead, F-box affinity for protein substrates is regulated through cdk/cyclin mediated phosphorylation of target proteins.
 * Skp1 - Bridging protein, forms part of the horseshoe-shaped complex, along with cullin (cul1). Skp1 is essential in the recognition and binding of the F-box.
 * Cullin (CUL1) forms the major structural scaffold of the SCF complex, linking the skp1 domain with the Rbx1 domain.
 * RBX1 - Rbx1 contains a small zinc-binding domain called the RING Finger, to which the E2-ubiquitin conjugate binds, allowing the transferral of the ubiquitin to a lysine residue on the target protein.

Progression of eukaryotic cell cycle is regulated through synthesis-degradation and phosphosylation-dephosohorylation of cell cycle regulating proteins. Two ubiquitin ligases are crucial in cell cycle. The anaphase-promoting complex or cyclosome (APC/C) controls metaphase-anaphase transition with its activator Cdc20. Its activity is required for sister chromatids separation. APC/C with another activator, Cdh1, is also active in G1 phase and controls levels of mitosis regulating proteins.

SCF controls G1/S through G2/M transitions. 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 human. SCF-Skp2 mainly ubiquitinates and degrades cyclin-dependent-kinase inhibitors (CKIs) such as p27 and p21 as well as G1/S cyclin, CyclinE, 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 (DSGXXS amino acid motif. X can be any amino acid) by kinases such as Polo-like kinase 1 (Plk1) and Cdk1-cyclinB. SCF-βTrCP and APC/C control each other to regulate timely cell cycle progression. Lists of substrates of SCF-Skp2 and -βTrCP are still growing.

Auxin stimulates binding of SCF-TIR1 to the AUX/IAA repressor, and its degradation, resulting in the activation of auxin-responsive genes. The TIR1 F-box protein acts as an auxin receptor and directly links auxin perception to degradation of the Aux/IAA proteins. TIR1 (Transport Inhibitor Response 1) is related to AFB (Auxin Signaling F-box).