CUL1 Gene: Function, Expression, Mutations, and Disease Associations | Cullin 1

CUL1 encodes cullin 1, a scaffold protein that forms the core of SCF (Skp1-Cullin-F-box) E3 ubiquitin ligase complexes. These complexes target specific proteins for ubiquitination and subsequent proteasomal degradation, regulating critical cellular processes including cell cycle progression, signal transduction, and transcription. CUL1 is essential for the degradation of key regulators such as cyclins, CDK inhibitors, and NF-κB pathway components.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• SCF complex assembly

• Ubiquitin mediated proteolysis (KEGG hsa04120)

• Cell cycle (KEGG hsa04110)

• p53 signaling pathway (KEGG hsa04115)

Cullin 1 is a 776-amino acid protein that serves as a molecular scaffold in SCF E3 ubiquitin ligases. It binds to the adaptor protein Skp1 and a RING finger protein (RBX1) to form the catalytic core, while an F-box protein provides substrate specificity. CUL1 undergoes neddylation, a post-translational modification that activates the complex. Through targeted ubiquitination, CUL1 controls degradation of cell cycle regulators (e.g., cyclin D1, p27), transcription factors (e.g., β-catenin, NF-κB), and other substrates, thereby influencing cell proliferation, survival, and differentiation.