دورية أكاديمية
Cdk5 phosphorylates Cdh1 and modulates cyclin B1 stability in excitotoxicity.
| العنوان: | Cdk5 phosphorylates Cdh1 and modulates cyclin B1 stability in excitotoxicity. |
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| المؤلفون: | Maestre C; Unidad de Investigación, Hospital Universitario de Salamanca, Instituto de Estudios de Ciencias de la Salud de Castilla y León, Salamanca, Spain., Delgado-Esteban M, Gomez-Sanchez JC, Bolaños JP, Almeida A |
| المصدر: | The EMBO journal [EMBO J] 2008 Oct 22; Vol. 27 (20), pp. 2736-45. Date of Electronic Publication: 2008 Sep 25. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8208664 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1460-2075 (Electronic) Linking ISSN: 02614189 NLM ISO Abbreviation: EMBO J Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2024- : [London] : Nature Publishing Group Original Publication: Eynsham, Oxford, England : Published for the European Molecular Biology Organization by IRL Press, [c1982- |
| مواضيع طبية MeSH: | Cadherins/*metabolism , Cyclin B/*metabolism , Cyclin-Dependent Kinase 5/*metabolism, Animals ; Apoptosis ; Cell Nucleus/metabolism ; Cells, Cultured ; Cyclin B1 ; Models, Biological ; Neurons/metabolism ; Phosphorylation ; Plasmids/metabolism ; Rats ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate/metabolism ; Serine/chemistry |
| مستخلص: | Anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase that destabilizes cell cycle proteins, is activated by Cdh1 in post-mitotic neurons, where it regulates axonal growth, synaptic plasticity and survival. The APC/C-Cdh1 substrate, cyclin B1, has been found to accumulate in degenerating brain areas in Alzheimer's disease and stroke. This highlights the importance of elucidating cyclin B1 regulation by APC/C-Cdh1 in neurons under stress conditions relevant to neurological disease. Here, we report that stimulation of N-methyl-D-aspartate receptors (NMDARs) that occurs in neurodegenerative diseases promoted the accumulation of cyclin B1 in the nuclei of cortical neurons; this led the neurons to undergo apoptotic death. Moreover, we found that the Ser-40, Thr-121 and Ser-163 triple phosphorylation of Cdh1 by the cyclin-dependent kinase-5 (Cdk5)-p25 complex was necessary and sufficient for cyclin B1 stabilization and apoptotic death after NMDAR stimulation. These results reveal Cdh1 as a novel Cdk5 substrate that mediates cyclin B1 neuronal accumulation in excitotoxicity. |
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| المشرفين على المادة: | 0 (Cadherins) 0 (Ccnb1 protein, rat) 0 (Cyclin B) 0 (Cyclin B1) 0 (Receptors, N-Methyl-D-Aspartate) 452VLY9402 (Serine) EC 2.7.11.1 (Cyclin-Dependent Kinase 5) |
| تواريخ الأحداث: | Date Created: 20080927 Date Completed: 20081117 Latest Revision: 20181113 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC2572178 |
| DOI: | 10.1038/emboj.2008.195 |
| PMID: | 18818692 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1460-2075 |
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| DOI: | 10.1038/emboj.2008.195 |