ROC1containing

ROC1containing refers to protein assemblies that include the ROC1 subunit, most commonly the RBX1 protein in humans or Roc1 in yeast. In eukaryotes, ROC1 is a core component of Cullin-RING ubiquitin ligases (CRLs), a family of E3 ubiquitin ligases that target a wide range of substrates for proteasomal degradation.

In CRLs, ROC1 binds to the Cullin scaffold and provides the RING finger domain that recruits the E2-conjugating enzyme and catalyzes ubiquitin transfer. Substrate specificity is provided by associated adaptors and receptors, such as F-box proteins in SCF complexes or DCAF/DDB1 in CRL4. This arrangement enables a modular system in which different substrate receptors direct ubiquitination to particular targets.

Functions of ROC1-containing complexes include regulation of cell cycle progression, DNA replication licensing, transcription factor turnover, and signaling pathways, achieved through ubiquitination of key regulatory proteins. By marking substrates for degradation, these complexes control timing and amplitude of cellular processes.

Regulation of ROC1-containing CRLs involves control of cullin neddylation, which activates the ligase, and deneddylation by the COP9 signalosome, which inactivates it. Post-translational modifications and expression levels of ROC1/RBX1 can also influence ligase activity and substrate selection, allowing dynamic responses to cellular conditions.

Clinical and research relevance: Abnormal ROC1-containing CRL activity has been linked to cancer and other diseases, making these complexes common targets in biomedical research and therapy development. Investigations employ methods such as co-immunoprecipitation, mass spectrometry, CRISPR-based gene perturbations, and in vitro ubiquitination assays to study their composition and function.