Substrate Structure Determines p97- and RAD23A/B-Mediated Proteasomal Degradation in Human Cells.

ABSTRACT: Proteasomal degradation of ubiquitinated proteins involves various accessory factors, including p97 and shuttle factors, but their requirements and relationship with substrate structural properties are not fully understood, especially in human cells. Here, we demonstrate that substrate structure dictates the dependency on p97 and RAD23A/B for proteasomal degradation in human cells, using two ubiquitin-fusion model substrates, Ub-GFP (well-folded) and Ub-GFP-tail (with an unstructured tail). Both substrates exhibited similar ubiquitin chain composition, primarily mediated by the UBR4-KCMF1 E3 ligase. Interactome analyses revealed that Ub-GFP preferentially interacts with p97 and RAD23B, while Ub-GFP-tail binds more strongly with the proteasome. The degradation of Ub-GFP depends on p97 and R

SUBMITTER: Ding Y 

PROVIDER: S-EPMC12552062 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature