Cullin-3 (CUL3)

Cullin-3 is a core scaffold protein of Cullin-RING E3 ubiquitin ligase complexes, fundamental to the ubiquitin–proteasome system that mediates the selective ubiquitination and proteasomal degradation of many proteins within the cell. CUL3 regulates a wide array of essential cellular processes—cell cycle progression, stress responses, protein trafficking, transcription, blood pressure regulation, and development—by recruiting various substrate-recognition proteins and linking them to the E2 ubiquitin-conjugating enzyme via the RING protein RBX1. Dynamic activation via neddylation (covalent attachment of the ubiquitin-like modifier NEDD8) is required for its ligase function. Genetic disruption of CUL3 leads to broad pathological effects, including neurodevelopmental disorders, hypertension, and cancer. CUL3 is studied as a potential therapeutic target and a biomarker, though direct pharmacologic inhibitors remain mostly investigational.

Other names

Cullin-3CUL3KIAA0617NEDAUSPHA2Ecullin-3

Inhibition of CUL3 neddylation → inhibition of E3 ubiquitin ligase activity (e.g., by NEDD8 pathway inhibitors). Modulation of protein homeostasis via altered substrate ubiquitination and degradation.