Active, Recombinant, Neddylated Human CUL2 / RBX1 Complex

Background: Cullin-2 (CUL2) is a central scaffold protein in CUL2-based Cullin-RING E3 ubiquitin ligase (CRL2) complexes that regulate the ubiquitylation and degradation of proteins involved in hypoxia signaling, cell cycle control, DNA damage responses, and developmental pathways. Within these complexes, CUL2 structurally bridges substrate-recognition adaptors containing Elongin B/C-binding motifs, such as the von Hippel-Lindau (VHL) tumor suppressor protein, with the RBX1 RING subunit, thereby positioning both the bound substrate and an E2 ubiquitin-conjugating enzyme to promote efficient ubiquitin transfer. Biologically, CUL2 plays a critical role in maintaining cellular proteostasis and regulating the turnover of key substrates including HIF-1α, and its dysregulation has been associated with cancer, developmental disorders, and altered cellular responses to hypoxia. In vivo, CUL2 E3 ligase activity depends on covalent attachment of NEDD8 (neddylation) to the CUL2 subunit, which activates the complex by promoting conformational changes that enhance E2 recruitment and ubiquitin transfer.