Cyclin-dependent Kinases Participate in Death of Neurons Evoked by DNA-damaging Agents
| العنوان: | Cyclin-dependent Kinases Participate in Death of Neurons Evoked by DNA-damaging Agents |
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| المؤلفون: | Jaya Padmanabhan, David S. Park, Michael L. Shelanski, Lloyd A. Greene, Erick J. Morris, Herbert M. Geller |
| المصدر: | The Journal of Cell Biology |
| بيانات النشر: | Rockefeller University Press, 1998. |
| سنة النشر: | 1998 |
| مصطلحات موضوعية: | Gene Expression Regulation, Viral, Antimetabolites, Antineoplastic, Ultraviolet Rays, DNA damage, CDK, Apoptosis, Superior Cervical Ganglion, Protein Serine-Threonine Kinases, neuronal, Rats, Sprague-Dawley, Cyclin-dependent kinase, Proto-Oncogene Proteins, CDC2-CDC28 Kinases, Animals, Cyclin D1, Kinase activity, Cells, Cultured, Cerebral Cortex, Neurons, biology, Cyclin-dependent kinase 4, Kinase, Cell Cycle, Cyclin-Dependent Kinase 2, Cyclin-dependent kinase 2, Cytarabine, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase 6, Cell Biology, Cell cycle, Antineoplastic Agents, Phytogenic, Cyclin-Dependent Kinases, Rats, Cell biology, Enzyme Activation, biology.protein, Camptothecin, Sindbis Virus, Cyclin-dependent kinase 6, Regular Articles |
| الوصف: | Previous reports have indicated that DNA-damaging treatments including certain anticancer therapeutics cause death of postmitotic nerve cells both in vitro and in vivo. Accordingly, it has become important to understand the signaling events that control this process. We recently hypothesized that certain cell cycle molecules may play an important role in neuronal death signaling evoked by DNA damage. Consequently, we examined whether cyclin-dependent kinase inhibitors (CKIs) and dominant-negative (DN) cyclin-dependent kinases (CDK) protect sympathetic and cortical neurons against DNA-damaging conditions. We show that Sindbis virus–induced expression of CKIs p16ink4, p21waf/cip1, and p27kip1, as well as DN-Cdk4 and 6, but not DN-Cdk2 or 3, protect sympathetic neurons against UV irradiation– and AraC-induced death. We also demonstrate that the CKIs p16 and p27 as well as DN-Cdk4 and 6 but not DN-Cdk2 or 3 protect cortical neurons from the DNA damaging agent camptothecin. Finally, in consonance with our hypothesis and these results, cyclin D1–associated kinase activity is rapidly and highly elevated in cortical neurons upon camptothecin treatment. These results suggest that postmitotic neurons may utilize Cdk4 and 6, signals that normally control proliferation, to mediate death signaling resulting from DNA-damaging conditions. |
| تدمد: | 1540-8140 0021-9525 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3fb2420f416235abc566ec850a0bb94bTest https://doi.org/10.1083/jcb.143.2.457Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3fb2420f416235abc566ec850a0bb94b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15408140 00219525 |
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