UbiREAD deciphers proteasomal degradation code of homotypic and branched K48 and K63 ubiquitin chains.

ABSTRACT: Ubiquitin chains define the fates of their modified proteins, often mediating proteasomal degradation in eukaryotes. Yet heterogeneity of intracellular ubiquitination has precluded systematically comparing the degradation capacities of different ubiquitin chains. We developed ubiquitinated reporter evaluation after intracellular delivery (UbiREAD), a technology that monitors cellular degradation and deubiquitination at high temporal resolution after bespoke ubiquitinated proteins are delivered into human cells. Comparing the degradation of a model substrate modified with various K48, K63, or K48/K63-branched ubiquitin chains revealed fundamental differences in their intracellular degradation capacities. K48 chains with three or more ubiquitins triggered degradation within minutes. K63-ubiq

SUBMITTER: Kiss L 

PROVIDER: S-EPMC7617769 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature