RBX1ROC1

RBX1, also known as ROC1 (Regulator of Cullins 1), is a small, evolutionarily conserved RING finger protein that serves as a core component of the SCF (Skp1-Cullin-F-box) E3 ubiquitin ligase complex in humans. As part of the SCF complex, RBX1 is responsible for recruiting and activating the ubiquitin-conjugating enzyme (E2), enabling transfer of ubiquitin to substrates bound by the associated F-box protein, thus marking them for proteasomal degradation. The activity of SCF ligases is regulated by neddylation of Cullin-1; RBX1 functions downstream of this modification to catalyze ubiquitination.

RBX1 contains a C-terminal RING finger domain that mediates interactions with E2 enzymes and a variable N-terminal region that contributes to Cullin-1 and Skp1 binding, allowing assembly of the active SCF complex. Substrate specificity is provided by the F-box protein component; RBX1 thus acts as a general platform for ubiquitin transfer rather than a substrate selector.

Physiological role: The SCF-RBX1 complex regulates degradation of multiple cell cycle regulators, helping control progression through G1/S and other transitions. Target substrates include cyclin-dependent kinase inhibitors and replication licensing factors, among others. Loss of RBX1 function impairs SCF activity and cell viability in many organisms.

Clinical relevance: Given its central role in protein turnover, dysregulation of RBX1 has been linked to cancer and proliferative disorders. Overexpression or altered regulation of RBX1 can promote degradation of tumor suppressors or cell cycle inhibitors, contributing to genomic instability and tumorigenesis. RBX1/ROC1 is studied as a potential target in strategies aiming to modulate ubiquitin ligase activity.