Figure 1.

(A) Composition of the CUL7 E3 Ub ligase complex. The CUL7 protein assembles an SCF-like complex composed of Skp1, Fbw8 and ROC1. While Fbw8 is responsible for substrate protein recognition, ROC1 recruits an Ub-charged E2 Ub-conjugating enzyme for substrate ubiquitination. It remains to be determined how CUL7 binds to the Skp1-Fbw8 heterodimer. (B) Domain organization of the CUL7 protein, as well as localization and relative frequency of CUL7 mutations identified in patients with 3-M (upper half) and Yakuts Short Stature syndrome (lower half). A single mutation (4582insT) of the CUL7 gene, predicted to yield a protein truncated at amino acid position 1553, was found in 43 patients of 37 families with Yakuts short stature syndrome. N8, abbreviation for Nedd8, denotes the CUL7 C-terminal site containing sequence conserved for cullin neddylation, as described previously.⁷⁵