Cullin-RING E3 Ubiquitin Ligase 7 in Growth Control and Cancer

CRL7^Fbxw8 is an E3 ubiquitin ligase complex, containing cullin7 (CUL7) as a scaffold, the F-box protein Fbxw8 as a substrate receptor, the Skp1 adaptor, and the ROC1/Rbx1 RING finger protein for working with E2 enzyme to facilitate ubiquitin transfer. This chapter provides an update on studies linking CRL7^Fbxw8 to hereditary human growth retardation disease, as at least 64 cul7 germ line mutations were found in patients with autosomal recessive 3-M syndrome. CRL7^Fbxw8 interacts with two additional 3-M associated proteins OBSL1 and CCDC8, leading to subcellular localization of the E3 complex to regions including plasma membrane, centrosome, and Golgi. At least ten mammalian cellular proteins were identified or implicated as CRL7^Fbxw8 substrates. Discussion focuses on the possible impact of CRL7^Fbxw8-mediated proteolytic or non-proteolytic pathways in growth control and cancer.