Cullin-1 (CUL1)

Cullin-1 is a highly conserved scaffold protein and the central component of the SCF (SKP1-CUL1-F-box) E3 ubiquitin ligase complex, a major regulator of protein degradation via the ubiquitin-proteasome system[1][4]. The SCF complex targets numerous regulatory proteins, including those controlling cell cycle progression (e.g., cyclins, p27), signal transduction, transcription, and primary ciliogenesis, thereby coordinating processes ranging from cell division and differentiation to chromosome maintenance and gene expression[1][3][4][5]. CUL1 undergoes neddylation, which is essential for its E3 ligase activity[1][2][4]. Abnormal CUL1 function is implicated in cancer, certain ciliopathies, neurodegenerative disease, and pathogen-host interactions, reflecting its fundamental biological roles and potential as a therapeutic target[3][4][5].

Other names

Cullin 1CUL1CUL-1cullin-1Lin-19-likeLin-19

Inhibitors of neddylation (e.g., pevonedistat) inactivate cullin-RING ligases by preventing neddylation of CUL1 and similar proteins, thereby blocking substrate ubiquitination and downstream proteasomal degradation[1][4]. Molecules targeting the assembly or function of the SCF complex affect degradation of cell cycle regulators, leading to cell cycle arrest or apoptosis[1][4].