دورية أكاديمية
The Caenorhabditis elegans CDT-2 ubiquitin ligase is required for attenuation of EGFR signalling in vulva precursor cells.
| العنوان: | The Caenorhabditis elegans CDT-2 ubiquitin ligase is required for attenuation of EGFR signalling in vulva precursor cells. |
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| المؤلفون: | Poulin, Gino B, Ahringer, Julie |
| بيانات النشر: | Springer Science and Business Media LLC //dx.doi.org/10.1186/1471-213x-10-109 BMC Dev Biol |
| سنة النشر: | 2011 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | Animals, Genetically Modified, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Endocytosis, Epistasis, Genetic, ErbB Receptors, Female, Gene Deletion, Humans, Ligases, RNA Interference, Receptors, Notch, Recombinant Fusion Proteins, Signal Transduction, Stem Cells, Ubiquitin-Protein Ligase Complexes, Ubiquitin-Protein Ligases, Vulva |
| الوصف: | BACKGROUND: Attenuation of the EGFR (Epidermal Growth Factor Receptor) signalling cascade is crucial to control cell fate during development. A candidate-based RNAi approach in C. elegans identified CDT-2 as an attenuator of LET-23 (EGFR) signalling. Human CDT2 is a component of the conserved CDT2/CUL4/DDB1 ubiquitin ligase complex that plays a critical role in DNA replication and G2/M checkpoint. Within this complex, CDT2 is responsible for substrate recognition. This ubiquitin ligase complex has been shown in various organisms, including C. elegans, to target the replication-licensing factor CDT1, and the CDK inhibitor p21. However, no previous link to EGFR signalling has been identified. RESULTS: We have characterised CDT-2's role during vulva development and found that it is a novel attenuator of LET-23 signalling. CDT-2 acts redundantly with negative modulators of LET-23 signalling and CDT-2 or CUL-4 downregulation causes persistent expression of the egl-17::cfp transgene, a marker of LET-23 signalling during vulva development. In addition, we show that CDT-2 physically interacts with SEM-5 (GRB2), a known negative modulator of LET-23 signalling that directly binds LET-23, and provide genetic evidence consistent with CDT-2 functioning at or downstream of LET-23. Interestingly, both SEM-5 and CDT-2 were identified independently in a screen for genes involved in receptor-mediated endocytosis in oocytes, suggesting that attenuation of LET-23 by CDT-2 might be through regulation of endocytosis. CONCLUSIONS: In this study, we have shown that CDT-2 and CUL-4, members of the CUL-4/DDB-1/CDT-2 E3 ubiquitin ligase complex attenuate LET-23 signalling in vulval precursor cells. In future, it will be interesting to investigate the potential link to endocytosis and to determine whether other signalling pathways dependent on endocytosis, e.g. LIN-12 (Notch) could be regulated by this ubiquitin ligase complex. This work has uncovered a novel function for the CUL-4/DDB-1/CDT-2 E3 ligase that may be relevant for its ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text/xml; application/pdf |
| اللغة: | English |
| العلاقة: | http://www.dspace.cam.ac.uk/handle/1810/237789Test |
| الإتاحة: | http://www.dspace.cam.ac.uk/handle/1810/237789Test |
| حقوق: | Poulin et al.; licensee BioMed Central Ltd. |
| رقم الانضمام: | edsbas.7E580C8C |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |