Academic Journal
Disruption of the COP9 Signalosome Csn2 Subunit in Mice Causes Deficient Cell Proliferation, Accumulation of p53 and Cyclin E
| العنوان: | Disruption of the COP9 Signalosome Csn2 Subunit in Mice Causes Deficient Cell Proliferation, Accumulation of p53 and Cyclin E |
|---|---|
| المؤلفون: | Early Embryonic Death, Karin Lykke-andersen, Laura Schaefer, Suchithra Menon, Xing-wang Deng, Jeffrey Boone Miller, Ning Wei |
| المساهمون: | The Pennsylvania State University CiteSeerX Archives |
| المصدر: | http://www.yale.edu/denglab/paper/Lykke-Andersen2003.pdf. |
| سنة النشر: | 2003 |
| المجموعة: | CiteSeerX |
| الوصف: | Csn2 (Trip15/Cops2/Alien) encodes the second subunit of the COP9 signalosome (CSN), an eight-subunit heteromeric complex homologous to the lid subcomplex of the 26S proteasome. CSN is a regulator of SCF (Skp1-cullin-F-box protein)ubiquitin ligases, mostly through the enzymatic activity that deconjugates the ubiquitin-like protein Nedd8 from the SCF Cul1 component. In addition, CSN associates with protein kinase activities targeting p53, c-Jun, and I�B for phosphorylation. Csn2 also interacts with and regulates a subset of nuclear hormone receptors and is considered a novel corepressor. We report that targeted disruption of Csn2 in mice caused arrest of embryo development at the peri-implantation stage. Csn2 �/ � blastocysts failed to outgrow in culture and exhibited a cell proliferation defect in inner cell mass, accompanied by a slight decrease in Oct4. In addition, lack of Csn2 disrupted the CSN complex and resulted in a drastic increase in cyclin E, supporting a role for CSN in cooperating with the SCF-ubiquitin-proteasome system to regulate protein turnover. Furthermore, Csn2 �/ � embryos contained elevated levels of p53 and p21, which may contribute to premature cell cycle arrest of the mutant. |
| نوع الوثيقة: | text |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.333.4419; http://www.yale.edu/denglab/paper/Lykke-Andersen2003.pdf |
| الاتاحة: | http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.333.4419 http://www.yale.edu/denglab/paper/Lykke-Andersen2003.pdf |
| Rights: | Metadata may be used without restrictions as long as the oai identifier remains attached to it. |
| رقم الانضمام: | edsbas.7E1B3158 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |