SCFCUL1

SCF-CUL1, often referred to as SCF-CUL1, denotes a class of multisubunit E3 ubiquitin ligases that use CUL1 as the central scaffold. The core complex comprises CUL1, RBX1 (or ROC1) as the catalytic subunit, Skp1 as an adaptor, and an interchangeable F-box protein that provides substrate specificity. The assembly allows the transfer of ubiquitin from an E2 enzyme to target substrates, marking them for degradation by the 26S proteasome.

The activity of SCF-CUL1 is tightly regulated. CUL1 undergoes a cycle of neddylation, the conjugation of NEDD8, which enhances ligase activity, and deneddylation, which reduces activity. The COP9 signalosome mediates deneddylation, providing a switch that modulates ubiquitination in response to cellular conditions. Substrate recognition is conferred by the F-box protein, which binds phosphorylated target proteins and recruits them to the ligase. This modular design allows SCF-CUL1 to regulate a broad set of substrates.

SCF-CUL1 targets include regulators of cell cycle progression, DNA replication licensing, and signal transduction. Examples of substrates are cyclin E, CDT1, p27 (CDKN1B), and other cell cycle regulators, with different F-box proteins (such as SKP2, FBXW7, and FBXO44) directing specificity. The complex is essential for proper cell cycle control in many organisms and has been implicated in development and tumorigenesis when dysregulated. Pharmacological inhibition of neddylation or disruption of SCF components is an area of active research, exploring potential anticancer strategies.