Reference - Detail
| RRC ID | 5949 |
|---|---|
| Author | Choe KP, Przybysz AJ, Strange K. |
| Title | The WD40 repeat protein WDR-23 functions with the CUL4/DDB1 ubiquitin ligase to regulate nuclear abundance and activity of SKN-1 in Caenorhabditis elegans. |
| Journal | Mol Cell Biol |
| Abstract |
The transcription factor SKN-1 protects Caenorhabditis elegans from stress and promotes longevity. SKN-1 is regulated by diverse signals that control metabolism, development, and stress responses, but the mechanisms of regulation and signal integration are unknown. We screened the C. elegans genome for regulators of cytoprotective gene expression and identified a new SKN-1 regulatory pathway. SKN-1 protein levels, nuclear accumulation, and activity are repressed by the WD40 repeat protein WDR-23, which interacts with the CUL-4/DDB-1 ubiquitin ligase to presumably target the transcription factor for proteasomal degradation. WDR-23 regulates SKN-1 target genes downstream from p38 mitogen-activated protein kinase, glycogen synthase kinase 3, and insulin-like receptor pathways, suggesting that phosphorylation of SKN-1 may function to modify its interaction with WDR-23 and/or CUL-4/DDB-1. These findings define the mechanism of SKN-1 accumulation in the cell nucleus and provide a new mechanistic framework for understanding how phosphorylation signals are integrated to regulate stress resistance and longevity. |
| Volume | 29(10) |
| Pages | 2704-15 |
| Published | 2009-5-1 |
| DOI | 10.1128/MCB.01811-08 |
| PII | MCB.01811-08 |
| PMID | 19273594 |
| PMC | PMC2682033 |
| MeSH | Amino Acid Sequence Animals Caenorhabditis elegans / cytology Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / classification Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Nucleus / metabolism* Cullin Proteins / genetics Cullin Proteins / metabolism* DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* Forkhead Transcription Factors Gene Expression Regulation Glutathione Transferase / genetics Glutathione Transferase / metabolism Humans Isoenzymes / genetics Isoenzymes / metabolism MAP Kinase Kinase 4 / genetics MAP Kinase Kinase 4 / metabolism Molecular Sequence Data Phylogeny Proteasome Endopeptidase Complex / metabolism Receptor, Insulin / genetics Receptor, Insulin / metabolism Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism Repetitive Sequences, Amino Acid* Repressor Proteins / classification Repressor Proteins / genetics Repressor Proteins / metabolism* Sequence Alignment Signal Transduction / physiology Stress, Physiological Transcription Factors / genetics Transcription Factors / metabolism* Two-Hybrid System Techniques |
| IF | 3.611 |
| Times Cited | 117 |
| WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| Resource | |
| C.elegans | tm1817 |