ROC1RBX1

Roc1Rbx1 is a conserved RING-box protein that functions as the catalytic subunit of Cullin-RING ubiquitin ligases, most notably the SCF (Skp1–Cullin–F-box) complex. In many species, Roc1 and RBX1 are used as synonyms for the same protein, and the term Roc1Rbx1 is sometimes used to describe the Roc1/RBX1 module that forms part of the SCF core together with Cullin-1 (CUL1), Skp1, and an F-box protein that provides substrate specificity.

Structure and mechanism

Roc1Rbx1 contains a RING finger domain of the C3HC4-type that coordinates a zinc ion, enabling interaction with Cullin-1 and the E2 ubiquitin-conjugating enzyme. The RING domain is essential for transferring ubiquitin from E2 to substrate, facilitating polyubiquitination and subsequent proteasomal degradation. As the catalytic component of the SCF ligase, Roc1Rbx1 works in concert with the scaffold Cul1, adaptor Skp1, and an F-box protein to recognize and process a wide range of substrates.

Biological role

SCF complexes regulate numerous cellular processes by marking specific proteins for degradation. This includes control of cell cycle progression, signal transduction, transcription, and other regulatory pathways. The repertoire of substrates is determined by the bound F-box protein, making Roc1Rbx1 a central element in maintaining cellular protein homeostasis.

Regulation and clinical relevance

SCF activity is modulated by the neddylation of Cullin-1, which activates the ligase, and by the availability of F-box proteins. Inhibitors that disrupt neddylation, such as pevonedistat, effectively inactivate CRLs including Roc1Rbx1-containing SCF complexes, a strategy explored in cancer therapy. Loss or dysregulation of Roc1Rbx1 function can disrupt proteostasis and contribute to disease, highlighting its significance in basic biology and clinical research.