دورية أكاديمية
Chemical-genetic analysis of cyclin dependent kinase 2 function reveals an important role in cellular transformation by multiple oncogenic pathways.
| العنوان: | Chemical-genetic analysis of cyclin dependent kinase 2 function reveals an important role in cellular transformation by multiple oncogenic pathways. |
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| المؤلفون: | Horiuchi D; Department of Medicine, University of California, San Francisco, CA 94143, USA., Huskey NE, Kusdra L, Wohlbold L, Merrick KA, Zhang C, Creasman KJ, Shokat KM, Fisher RP, Goga A |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2012 Apr 24; Vol. 109 (17), pp. E1019-27. Date of Electronic Publication: 2012 Apr 03. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : National Academy of Sciences |
| مواضيع طبية MeSH: | Cell Transformation, Neoplastic* , Oncogenes*, Cyclin-Dependent Kinase 2/*physiology, Animals ; Cell Adhesion ; Cell Line, Tumor ; Cell Proliferation ; Colonic Neoplasms/enzymology ; Colonic Neoplasms/pathology ; Cyclin-Dependent Kinase 2/antagonists & inhibitors ; Cyclin-Dependent Kinase 2/chemistry ; Cyclin-Dependent Kinase 2/genetics ; Gene Knockdown Techniques ; Humans ; Mice ; RNA, Small Interfering |
| مستخلص: | A family of conserved serine/threonine kinases known as cyclin-dependent kinases (CDKs) drives orderly cell cycle progression in mammalian cells. Prior studies have suggested that CDK2 regulates S-phase entry and progression, and frequently shows increased activity in a wide spectrum of human tumors. Genetic KO/knockdown approaches, however, have suggested that lack of CDK2 protein does not prevent cellular proliferation, both during somatic development in mice as well as in human cancer cell lines. Here, we use an alternative, chemical-genetic approach to achieve specific inhibition of CDK2 kinase activity in cells. We directly compare small-molecule inhibition of CDK2 kinase activity with siRNA knockdown and show that small-molecule inhibition results in marked defects in proliferation of nontransformed cells, whereas siRNA knockdown does not, highlighting the differences between these two approaches. In addition, CDK2 inhibition drastically diminishes anchorage-independent growth of human cancer cells and cells transformed with various oncogenes. Our results establish that CDK2 activity is necessary for normal mammalian cell cycle progression and suggest that it might be a useful therapeutic target for treating cancer. |
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| معلومات مُعتمدة: | EB001987 United States EB NIBIB NIH HHS; CA136717 United States CA NCI NIH HHS; United States HHMI Howard Hughes Medical Institute; GM056985 United States GM NIGMS NIH HHS; R01 CA136717 United States CA NCI NIH HHS; R01 EB001987 United States EB NIBIB NIH HHS; R01 GM056985 United States GM NIGMS NIH HHS |
| المشرفين على المادة: | 0 (RNA, Small Interfering) EC 2.7.11.22 (Cyclin-Dependent Kinase 2) |
| تواريخ الأحداث: | Date Created: 20120405 Date Completed: 20120709 Latest Revision: 20211021 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC3340028 |
| DOI: | 10.1073/pnas.1111317109 |
| PMID: | 22474407 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1091-6490 |
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| DOI: | 10.1073/pnas.1111317109 |