論文 - 詳細
| RRC ID | 18678 |
|---|---|
| 著者 | Liu C, Poitelea M, Watson A, Yoshida SH, Shimoda C, Holmberg C, Nielsen O, Carr AM. |
| タイトル | Transactivation of Schizosaccharomyces pombe cdt2+ stimulates a Pcu4-Ddb1-CSN ubiquitin ligase. |
| ジャーナル | EMBO J |
| Abstract |
Cullin-4 forms a scaffold for multiple ubiquitin ligases. In Schizosaccharomyces pombe, the Cullin-4 homologue (Pcu4) physically associates with Ddb1 and the COP9 signalosome (CSN). One target of this complex is Spd1. Spd1 regulates ribonucleotide reductase (RNR) activity. Spd1 degradation during S phase, or following DNA damage of G2 cells, results in the nuclear export of the small RNR subunit. We demonstrate that Cdt2, an unstable WD40 protein, is a regulatory subunit of Pcu4-Ddb1-CSN ubiquitin ligase. cdt2 deletion stabilises Spd1 and prevents relocalisation of the small RNR subunit from the nucleus to the cytoplasm. cdt2+ is periodically transcribed by the Cdc10/DSC1 transcription factor during S phase and transiently transcribed following DNA damage of G2 cells, corresponding to Spd1 degradation profiles. Cdt2 co-precipitates with Spd1, and Cdt2 overexpression results in constitutive Spd1 degradation. We propose that Cdt2 incorporation into the Pcu4-Ddb1-CSN complex prompts Spd1 targeting and subsequent degradation and that Cdt2 is a WD40 repeat adaptor protein for Cullin-4-based ubiquitin ligase. |
| 巻・号 | 24(22) |
| ページ | 3940-51 |
| 公開日 | 2005-11-16 |
| DOI | 10.1038/sj.emboj.7600854 |
| PII | 7600854 |
| PMID | 16252005 |
| PMC | PMC1283953 |
| MeSH | Adaptor Proteins, Signal Transducing / genetics Adaptor Proteins, Signal Transducing / metabolism* COP9 Signalosome Complex Cell Cycle / physiology Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism* Cullin Proteins / genetics Cullin Proteins / metabolism DNA Damage DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* Enzyme Activation Humans Multiprotein Complexes / genetics Multiprotein Complexes / metabolism* Peptide Hydrolases / genetics Peptide Hydrolases / metabolism* Protein Subunits / genetics Protein Subunits / metabolism Schizosaccharomyces / genetics Schizosaccharomyces / physiology Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / metabolism* Transcription, Genetic Transcriptional Activation* Ubiquitin-Protein Ligase Complexes / genetics Ubiquitin-Protein Ligase Complexes / metabolism* |
| IF | 9.889 |
| 引用数 | 75 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| リソース情報 | |
| 酵母 | |