Skpl/Cull/F-Box Protein Complex

The essential components of the SCF ubiquitin E3 ligase include Skpl, Cul-1/ Cdc53, one of many F-box proteins, and the RINC-H2-finger protein Rod (Rbxl or Hrtl) (Figure 6.2). Although initial studies did not reveal the presence of a fourth component of the SCF complex [14, 15], later work showed that a RINC-H2-finger protein, Rod, is an essential subunit of the SCF complex [3]. The SCF complex thus contains three invariable components (Rod, Cull, and Skpl) which provide a core structure to which one of the many substrate-specific subunits (F-box proteins) binds. The Rocl-Cull-Skpl core also independently interacts with the ubiquitin E2-conjugating enzyme to couple ubiquitin transfer to the substrates [3]. One of the E-box proteins binds directly to a specific substrate and such interaction facilitates the polyubiquitination of the substrate by ubiquitin... 

The role of Skpl is to bring the substrate-targeting subunit, the F-box protein, into proximity with the Cull/Rocl/E2 complex to promote ubiquitin transfer from the E2-ubiquitin to the F-box protein-bound substrates. 

Another level of control is mediated through the control of F-box protein stabilities by the SCF complex using an auto-ubiquitination mechanism. Deletion of the F-box motif of various F-box proteins such as yeast Cdc4 or j5-Trcp abolishes the interaction between Skpl/Cull and the F-box proteins [66]. Consequently the F-box proteins become more stable. This regulation may provide a means to recycle the components of SCF complexes between different F-box proteins. In addition, the levels of a particular F-box protein may be in part regulated by the balance between autoubiquitination and substrate-specific ubiquitination and thus could be sensitive to the presence of the substrates. 

Lyapina, S. A., Correll, C. C., Kipreos, E. T., and Deshaies, R. J. (1998). Human CULl forms an evolutionarily conserved ubiquitin ligase complex (SCF) with SKPl and an F-box protein, Proc Natl Acad Sci U S A 95,7451-6. 

Fig. 2.15 Structure and function of the SCF complex. The SCF complex was originally identified as a heterotrimer composed of Skpl, Cull and an F-box protein. A fourth component, the RING finger pro-...

Fig. 13.13 Role of the SCF complex as a versatile E3 ubiquitin ligase. The SCF complex is composed ofthe proteins Skpl, Cull, The RING-finger protein Rbxl and an F-box protein. Each F-box protein contains an F-box domain, which is required for binding to Skpl, as well as a specific substrate recognition motif. Ubiquitin is transferred from E2 to the substrate with the help ofthe SCF complex. Whereas Skpl, Cull and Rbxl are invariable com-...

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