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.[1]

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

Progression of eukaryotic cell cycle is regulated through synthesis-degradation and phosphorylation-dephosphorylation 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 [2]. Therefore SCF-Skp2 promotes cell cycle progression and cell growth [3]. 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[4]. 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).

References

  1. ^ Morgan, David "Protein Degradation in Cell-Cycle Control", The Cell Cycle; Principles of Control 2007
  2. ^ David Frescas and Michele Pagano (2008). “Deregulated proteolysis by the F‑box proteins SKP2 and β‑TrCP: tipping the scales of cancer’, NATURE REVIEWS cancer 8 (441).
  3. ^ Keiichi I. Nakayama and Keiko Nakayama (2005). “Regulation of the cell cycle by SCF-type ubiquitin ligases”, Seminars in Cell & Developmental Bioloby, 16 (323).
  4. ^ Hartmut C. Vodermaier (2004). “APC/C and SCF: Controlling Each Other and the Cell Cycle”, Current Biology, 14 (787)