Cyclin-dependent kinase inhibitor indirubin-3'-oxime selectively inhibits human papillomavirus type 16 E7-induced numerical centrosome anomalies
| Autor: | Pies, T., K. J., Schaper, Leost, M., D. W., Zaharevitz, Gussio, R., Meijer, L., Kunicke, C. |
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| Přispěvatelé: | Molécules et cibles thérapeutiques (MCT), Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Tumor *Centrosome Cyclin-Dependent Kinases/*antagonists & inhibitors Enzyme Inhibitors/*pharmacology Humans Indoles/*pharmacology Oncogene Proteins
Non-U.S. Gov't S Phase Viral/*antagonists & inhibitors/physiology Oximes/*pharmacology Rna Research Support Base Sequence Cell Line [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology |
| Zdroj: | Oncogene Oncogene, Nature Publishing Group, 2004, 23, pp.8206-8215 Oncogene, 2004, 23, pp.8206-8215 |
| ISSN: | 0950-9232 1476-5594 |
| Popis: | Dysregulation of the centrosome duplication cycle has been implicated in tumorigenesis. Our previous work has shown that the human papillomavirus type 16 (HPV-16) E7 oncoprotein rapidly induces aberrant centrosome and centriole duplication in normal human cells. We report here that HPV E7-induced abnormal centriole duplication is specifically abrogated by a small molecule CDK inhibitor, indirubin-3'-oxime (IO), but not a kinase-inactive derivative. Importantly, normal centriole duplication was not markedly affected by IO, and the inhibitory effects were observed at concentrations that did not affect the G1/S transition of the cell division cycle. Depletion of CDK2 by siRNA similarly abrogated HPV E7-induced abnormal centrosome duplication and ectopic expression of CDK2 in combination with cyclin E or cyclin A could rescue the inhibitory effect of IO. IO treatment also reduced the steady-state level of aneuploid cells in HPV-16 E7-expressing cell populations. Our results suggest that cyclin/CDK2 activity is critically involved in abnormal centrosome duplication induced by HPV-16 E7 oncoprotein expression, but may be dispensable for normal centrosome duplication and cell cycle progression. |
| Databáze: | OpenAIRE |
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