| Autor: |
Vishnu Balaji, Leonie Müller, Robin Lorenz, Éva Kevei, William H. Zhang, Ulises Santiago, Jan Gebauer, Ernesto Llamas, David Vilchez, Carlos J. Camacho, Wojciech Pokrzywa, Thorsten Hoppe |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Molecular cell. 82(17) |
| ISSN: |
1097-4164 |
| Popis: |
The high substrate selectivity of the ubiquitin/proteasome system is mediated by a large group of E3 ubiquitin ligases. The ubiquitin ligase CHIP regulates the degradation of chaperone-controlled and chaperone-independent proteins. To understand how CHIP mediates substrate selection and processing, we performed a structure-function analysis of CHIP and addressed its physiological role in Caenorhabditis elegans and human cells. The conserved function of CHIP in chaperone-assisted degradation requires dimer formation to mediate proteotoxic stress resistance and to prevent protein aggregation. The CHIP monomer, however, promotes the turnover of the membrane-bound insulin receptor and longevity. The dimer-monomer transition is regulated by CHIP autoubiquitylation and chaperone binding, which provides a feedback loop that controls CHIP activity in response to cellular stress. Because CHIP also binds other E3 ligases, such as Parkin, the molecular switch mechanism described here could be a general concept for the regulation of substrate selectivity and ubiquitylation by combining different E3s. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
