Transactivation of Schizosaccharomyces pombe cdt2+ stimulates a Pcu4–Ddb1–CSN ubiquitin ligase
| Autor: | Marius Poitelea, Adam T. Watson, Antony M. Carr, Cong Liu, Olaf Nielsen, Christian Holmberg, Shuhei Yoshida, Chikashi Shimoda |
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| Rok vydání: | 2005 |
| Předmět: |
Transcriptional Activation
Transcription Genetic Cell Cycle Proteins Biology Article General Biochemistry Genetics and Molecular Biology DDB1 Ubiquitin Schizosaccharomyces Humans COP9 signalosome Molecular Biology Adaptor Proteins Signal Transducing General Immunology and Microbiology COP9 Signalosome Complex General Neuroscience Cell Cycle Ubiquitin-Protein Ligase Complexes Cullin Proteins biology.organism_classification Molecular biology Ubiquitin ligase DNA-Binding Proteins Enzyme Activation Protein Subunits Ribonucleotide reductase Multiprotein Complexes Schizosaccharomyces pombe biology.protein Schizosaccharomyces pombe Proteins Cullin DNA Damage Peptide Hydrolases |
| Zdroj: | The EMBO Journal. 24:3940-3951 |
| ISSN: | 1460-2075 0261-4189 |
| DOI: | 10.1038/sj.emboj.7600854 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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