Regulation of protein quality control by UBE4B and LSD1 through p53-mediated transcription.
PLoS Biol
; 13(4): e1002114, 2015 Apr.
Article
in En
| MEDLINE
| ID: mdl-25837623
ABSTRACT
Protein quality control is essential for clearing misfolded and aggregated proteins from the cell, and its failure is associated with many neurodegenerative disorders. Here, we identify two genes, ufd-2 and spr-5, that when inactivated, synergistically and robustly suppress neurotoxicity associated with misfolded proteins in Caenorhabditis elegans. Loss of human orthologs ubiquitination factor E4 B (UBE4B) and lysine-specific demethylase 1 (LSD1), respectively encoding a ubiquitin ligase and a lysine-specific demethylase, promotes the clearance of misfolded proteins in mammalian cells by activating both proteasomal and autophagic degradation machineries. An unbiased search in this pathway reveals a downstream effector as the transcription factor p53, a shared substrate of UBE4B and LSD1 that functions as a key regulator of protein quality control to protect against proteotoxicity. These studies identify a new protein quality control pathway via regulation of transcription factors and point to the augmentation of protein quality control as a wide-spectrum antiproteotoxicity strategy.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Quality Control
/
Transcription, Genetic
/
Tumor Suppressor Protein p53
/
Caenorhabditis elegans
/
Caenorhabditis elegans Proteins
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
PLoS Biol
Journal subject:
BIOLOGIA
Year:
2015
Type:
Article
Affiliation country:
United States