| RRC ID |
45624
|
| Author |
Periz G, Lu J, Zhang T, Kankel MW, Jablonski AM, Kalb R, McCampbell A, Wang J.
|
| Title |
Regulation of protein quality control by UBE4B and LSD1 through p53-mediated transcription.
|
| Journal |
PLoS Biol
|
| 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.
|
| Volume |
13(4)
|
| Pages |
e1002114
|
| Published |
2015-4-1
|
| DOI |
10.1371/journal.pbio.1002114
|
| PII |
PBIOLOGY-D-14-04412
|
| PMID |
25837623
|
| PMC |
PMC4383508
|
| MeSH |
Animals
Autophagy
Caenorhabditis elegans / genetics*
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / metabolism*
Gene Knockdown Techniques
Mutation
Proteasome Endopeptidase Complex / metabolism
Quality Control*
Stress, Physiological
Superoxide Dismutase / genetics
Superoxide Dismutase-1
Transcription, Genetic / physiology*
Tumor Suppressor Protein p53 / physiology*
|
| IF |
7.076
|
| Times Cited |
21
|
|
WOS Category
|
BIOLOGY
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| C.elegans |
tm1380 |
