The cullin family of ubiquitin ligases can potentially assemble hundreds of RING-type E3 complexes (CRLs) by utilizing different substrate receptors that share common interaction domains. Cullin receptors dictate substrate specificity, and cullin-mediated substrate degradation controls a wide range of cellular processes, including proliferation, differentiation, and apoptosis. Dysregulation of cullin activity has been shown to contribute to oncogenesis through the accumulation of oncoproteins or the excessive degradation of tumor suppressors. In this review, we will discuss cullin complexes and their substrates, the regulatory pathways that affect cullin activity, and the mechanisms by which cullins may facilitate or inhibit carcinogenesis.
