The 26S proteasome substrates and the dynamics of nuclear proteome upon DNA damage
Ontology highlight
ABSTRACT: Upon DNA damage, numerous proteins are targeted for ubiquitin-dependent proteasomal degradation. We show that phosphorylation of Rpn10/PSMD4 (ubiquitin receptor of the proteasome) at Ser266, is required for DNA repair. Here, we performed TurboID proximity labeling for capturing the proteasome substrates under DNA damage. Numerous proteins which involve in DNA damage response, chromosome reorganization cell cycle and histone modification were identified as the potential pronuteasome substrates. We find that DNA damage reduced the overall affinity between substrates and wild-type Rpn10 compared to Rpn10-Ser266 mutant cells. Combining TMT quantitative proteomic studies, we observed the dynamics of more than 2,000 nuclear proteins upon DNA damage and time course release. Most proteins were accumulated in wild-type cells in the time course release, while the Rpn10-Ser266 mutant cells show almost no changes in protein level. These findings reveal an inherent self-limiting mechanism of the proteasome that, by controlling substrate recognition through Rpn10 phosphorylation, fine-tunes protein degradation for optimal responses under stress.
ORGANISM(S): Homo Sapiens
SUBMITTER: Xing Guo
PROVIDER: PXD047298 | iProX | Tue Nov 28 00:00:00 GMT 2023
REPOSITORIES: iProX
ACCESS DATA