Gabriela Prus (Copenhagen / DK), Shankha Satpathy (Copenhagen / DK), Brian Weinert (Copenhagen / DK), Takeo Narita (Copenhagen / DK), Chunaram Choudhary (Copenhagen / DK)
Ubiquitylation regulates most proteins and biological processes in a eukaryotic cell. However, the site-specific occupancy (stoichiometry) and turnover rate of ubiquitylation have not been quantified. Here we present an integrated picture of the global ubiquitylation site occupancy and half-life. Ubiquitylation site occupancy spans over four orders of magnitude, but the median ubiquitylation site occupancy is three orders of magnitude lower than that of phosphorylation. The occupancy, turnover rate, and regulation of sites by proteasome inhibitors are strongly interrelated, and these attributes distinguish sites involved in proteasomal degradation and cellular signaling. Sites in structured protein regions exhibit longer half-lives and stronger upregulation by proteasome inhibitors than sites in unstructured regions. Importantly, we discovered a surveillance mechanism that rapidly and site-indiscriminately deubiquitylates all ubiquitin-specific E1 and E2 enzymes, protecting them against accumulation of bystander ubiquitylation. The work provides a systems-scale, quantitative view of ubiquitylation properties and reveals general principles of ubiquitylation-dependent governance.
We use cookies on our website. Cookies are small (text) files that are created and stored on your device (e.g., smartphone, notebook, tablet, PC). Some of these cookies are technically necessary to operate the website, other cookies are used to extend the functionality of the website or for marketing purposes. Apart from the technically necessary cookies, you are free to allow or not allow cookies when visiting our website.