論文 - 詳細
| RRC ID | 3594 |
|---|---|
| 著者 | Kim Y, Kipreos ET. |
| タイトル | The Caenorhabditis elegans replication licensing factor CDT-1 is targeted for degradation by the CUL-4/DDB-1 complex. |
| ジャーナル | Mol Cell Biol |
| Abstract |
The replication of genomic DNA is strictly regulated to occur only once per cell cycle. This regulation centers on the temporal restriction of replication licensing factor activity. Two distinct ubiquitin ligase (E3) complexes, CUL4/DDB1 and SCF(Skp2), have been reported to target the replication licensing factor Cdt1 for ubiquitin-mediated proteolysis. However, it is unclear to what extent these two distinct Cdt1 degradation pathways are conserved. Here, we show that Caenorhabditis elegans DDB-1 is required for the degradation of CDT-1 during S phase. DDB-1 interacts specifically with CUL-4 but not with other C. elegans cullins. A ddb-1 null mutant exhibits extensive DNA rereplication in postembryonic BLAST cells, similar to what is observed in cul-4(RNAi) larvae. DDB-1 physically associates with CDT-1, suggesting that CDT-1 is a direct substrate of the CUL-4/DDB-1 E3 complex. In contrast, a deletion mutant of the C. elegans Skp2 ortholog, skpt-1, appears overtly wild type with the exception of an impenetrant gonad migration defect. There is no appreciable role for SKPT-1 in the degradation of CDT-1 during S phase, even in a sensitized ddb-1 mutant background. We propose that the CUL-4/DDB-1 ubiquitin ligase is the principal E3 for regulating the extent of DNA replication in C. elegans. |
| 巻・号 | 27(4) |
| ページ | 1394-406 |
| 公開日 | 2007-2-1 |
| DOI | 10.1128/MCB.00736-06 |
| PII | MCB.00736-06 |
| PMID | 17145765 |
| PMC | PMC1800708 |
| MeSH | Alleles Animals Caenorhabditis elegans / cytology Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / metabolism* Cyclin-Dependent Kinase Inhibitor Proteins / metabolism Female Gene Deletion Gene Expression Regulation, Developmental Germ Cells / growth & development Humans Larva / cytology Ligases / chemistry Ligases / metabolism* Phenotype Protein Binding Protein Processing, Post-Translational* S Phase* S-Phase Kinase-Associated Proteins / metabolism Vulva / cytology Vulva / growth & development |
| IF | 3.611 |
| 引用数 | 39 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| 線虫 | tm1769 tm2212 |