Fig. 1. Schematic representations of different cullin RING ubiquitin ligases and the APC/C. All cullin complexes are Nedd8 modified (see Box 2) and recruit E2-bound ubiquitin through their association with the RING-finger protein Rbx1. (A) The SCF complex is the best-characterized cullin ligase. Cullin 1 proteins bind at their N terminus to the BTB-fold protein Skp1. Skp1, in return, interacts with different F-box proteins, which specifically recognize substrates (blue). (B) Cullin 2-based ECS complexes recruit their substrate through their interaction with elongin B and elongin C and a variable SOCS-box protein, such as ZIF-1 (hence the name ECS complex). (C) Cullin 3-based complexes are unique in using only one protein to bind the cullin and the substrate. (D) The APC/C has many more subunits than the cullin ligases, many of which have not been assigned a function and are shown as a single yellow mass. Although not Nedd8 modified, APC2 has sequence similarity to cullin proteins and interacts with the APC11 RING-finger protein. Different WD40 repeat proteins, e.g. Cdc20 or Cdh1, mediate substrate recognition by the APC/C. APC/C, anaphase promoting complex/cyclosome; BTB, Bric-a-Brack, Tramtrack and Brahma; Cdc20, cell division cycle 20; Cdh1, Cdc20 homolog 1; ECS, elongin B/C, cullin 2, SOCS box; MEI-1, meiosis defective 1; MEL-26, maternal effect lethal; Rbx1, ring box protein 1; SCF, Skp1, cullin 1 and F-box subunits; Skp1, suppressor of kinetochore protein 1; ZIF-1, zinc-finger interacting factor 1.