The SCF Ubiquitin E3 Ligase

Cullin-1 (Cull) was originally isolated from Caenorhahditis elegans as a negative regulator of cell proliferation during development [13]. Loss of Cull (or Un-19) in 

Skp2 DSLPDELLLGIFSCLCLPELLKVSGVCKRWYRLASD-ESLW (a. a. 98-137) Cdc4 tslpfeislkifnylqfediinslgvsqnwnkiirkstslw (a.a.276-316) CycF LSLPEDVLFHILKWLSVEDILAVRAVHSQI KDLVDNHASVW (a. a. 33-73) 

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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... 

F-box proteins serve as the substrate-targeting subunit of the SCF ubiquitin E3 ligase [5]. They are structurally diverse but they all contain a relatively conserved signature motif of about 45-50 amino acids [5]. This motif, the F-box, was initially... 

Elucidation of the structure of the SCF ubiquitin E3 ligase complex and their substrates should help resolve certain issues regarding the mechanism by which SCF E3 ligase promotes ubiquitin transfer from the E2 enzyme to the protein substrate. Recently, the structures of Cull/Rocl in complex with Skpl and Skp2, as well as that of Skpl/jS-Trcp and Cdc4, have been reported [21, 25, 55, 56]. These studies... 

Fig. 6.2. The structures of SCF, Cul2-Elongin B-C, and Cul3-BTB/POZ ubiquitin E3 ligase complexes with the bound substrates and E2 enzymes.

The SCF Complex and the Related Cullin-containing Ubiquitin E3 Ligase 1151... 

Mamillapalli, R., et al., PTEN regulates the ubiquitin-dependent degradation of the CDK inhibitor p27(KIPl) through the ubiquitin E3 ligase SCF(SKP2). Curr Biol, 2001, 11(4), 263-7. 

The SCF, a ubiquitin ligase complex, consists of the piimaiy subunits Skpl, Cullin and Rbx/Rocl. While the Rbx/Cul components form the E3 ligase catalytic core... 

Both genetic and biochemical analyses suggest that the SCF E3 ligase targets a wide spectrum of important proteins for ubiquitin-dependent proteolysis (see Table 6.1 for examples). A common feature of the physiological substrates of various SCF... 

Noueeddine, M. a., et al., Drosophila Rocla encodes a RING-H2 protein with a unique function in processing the Hh signal transducer Ci by the SCF E3 ubiquitin ligase. Dev Cell,... 

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