English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Receptor oligomerization guides pathway choice between proteasomal and autophagic degradation.

Lu, K., den Brave, F., & Jentsch, S. (2017). Receptor oligomerization guides pathway choice between proteasomal and autophagic degradation. Nature cell biology, 19(6), 732-739. doi:10.1038/ncb3531.

Item is

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Lu, Kefeng1, Author              
den Brave, Fabian1, Author              
Jentsch, Stefan1, Author              
Affiliations:
1Jentsch, Stefan / Molecular Cell Biology, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565156              

Content

show
hide
Free keywords: -
 Abstract: Abnormal or aggregated proteins have a strong cytotoxic potential and are causative for human disorders such as Alzheimer's, Parkinson's, Huntington's disease and amyotrophic lateral sclerosis. If not restored by molecular chaperones, abnormal proteins are typically degraded by proteasomes or eliminated by selective autophagy. The discovery that both pathways are initiated by substrate ubiquitylation but utilize different ubiquitin receptors incited a debate over how pathway choice is achieved. Here, we demonstrate in yeast that pathway choice is made after substrate ubiquitylation by competing ubiquitin receptors harbouring either proteasome- or autophagy-related protein 8 (Atg8/LC3)-binding modules. Proteasome pathway receptors bind ubiquitin moieties more efficiently, but autophagy receptors gain the upper hand following substrate aggregation and receptor bundling. Indeed, by using sets of modular artificial receptors harbouring identical ubiquitin-binding modules we found that proteasome/autophagy pathway choice is independent of the ubiquitin-binding properties of the receptors but largely determined by their oligomerization potentials. Our work thus suggests that proteasomal degradation and selective autophagy are two branches of an adaptive protein quality control pathway, which uses substrate ubiquitylation as a shared degradation signal.

Details

show
hide
Language(s): eng - English
 Dates: 2017-05-152017
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 28504708
DOI: 10.1038/ncb3531
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Nature cell biology
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 19 (6) Sequence Number: - Start / End Page: 732 - 739 Identifier: ISSN: 1476-4679