دورية أكاديمية
Why minimal is not optimal: driving the mammalian cell cycle--and drug discovery--with a physiologic CDK control network.
| العنوان: | Why minimal is not optimal: driving the mammalian cell cycle--and drug discovery--with a physiologic CDK control network. |
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| المؤلفون: | Merrick KA; Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, NY, USA., Fisher RP |
| المصدر: | Cell cycle (Georgetown, Tex.) [Cell Cycle] 2012 Jul 15; Vol. 11 (14), pp. 2600-5. Date of Electronic Publication: 2012 Jul 15. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Taylor & Francis Country of Publication: United States NLM ID: 101137841 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1551-4005 (Electronic) Linking ISSN: 15514005 NLM ISO Abbreviation: Cell Cycle Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2015- : Philadelphia, PA : Taylor & Francis Original Publication: Georgetown, TX : Landes Bioscience, c2002- |
| مواضيع طبية MeSH: | Cyclin-Dependent Kinases/*metabolism, Cyclin-Dependent Kinase 2/metabolism ; Cyclin-Dependent Kinases/antagonists & inhibitors ; Cyclins/metabolism ; Drug Evaluation, Preclinical ; G1 Phase ; Gene Targeting ; HCT116 Cells ; Humans ; S Phase |
| مستخلص: | Progression through the eukaryotic cell division cycle is governed by the activity of cyclin-dependent kinases (CDKs). For a CDK to become active it must (1) bind a positive regulatory subunit (cyclin) and (2) be phosphorylated on its activation (T) loop. In metazoans, multiple CDK catalytic subunits, each with a distinct set of preferred cyclin partners, regulate the cell cycle, but it has been difficult to assign functions to individual CDKs in vivo. Biochemical analyses and experiments with dominant-negative alleles suggested that specific CDK/cyclin complexes regulate different events, but genetic loss of interphase CDKs (Cdk2, -4 and -6), alone or in combination, did not block proliferation of cells in culture. These knockout and knockdown studies suggested redundancy or plasticity built into the CDK network but did not address whether there was true redundancy in normal cells with a full complement of CDKs. Here, we discuss recent work that took a chemical-genetic approach to reveal that the activity of a genetically non-essential CDK, Cdk2, is required for cell proliferation when normal cyclin pairing is maintained. These results have implications for the systems-level organization of the cell cycle, for regulation of the restriction point and G 1/S transition and for efforts to target Cdk2 therapeutically in human cancers. |
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| معلومات مُعتمدة: | R01 GM056985 United States GM NIGMS NIH HHS; GM056985 United States GM NIGMS NIH HHS |
| المشرفين على المادة: | 0 (Cyclins) EC 2.7.11.22 (Cyclin-Dependent Kinase 2) EC 2.7.11.22 (Cyclin-Dependent Kinases) |
| تواريخ الأحداث: | Date Created: 20120627 Date Completed: 20121126 Latest Revision: 20211021 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC3409006 |
| DOI: | 10.4161/cc.20758 |
| PMID: | 22732498 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1551-4005 |
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| DOI: | 10.4161/cc.20758 |