| Geldanamycin induces G2 arrest in U87MG glioblastoma cells through downregulation of Cdc2 and cyclin B1. | |
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MedLine Citation:
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PMID: 17324379 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cell cycle progression requires precise expression and activation of several cyclins and cyclin-dependent kinases. Geldanamycin (GA) affects cell cycle progression in various kinds of cells. We analyzed GA-induced cell cycle regulation in glioblastoma cells. GA-induced G2 or M arrest in glioblastoma cells in a cell line-dependent manner. GA decreased the expression of Cdc2 and cyclin B1 in U87MG cells. And phosphorylated Cdc2 decreased along with Cdc2 in the GA-treated cells. This cell line showed G2 arrest after GA treatment. In contrast, GA failed to down-regulate these cell cycle regulators in U251MG cells. In U251MG cells, the cell cycle was arrested at M phase in addition to G2 by GA. Next, we analyzed the mechanism of the GA-induced regulation of Cdc2 and cyclin B1 in U87MG cells. Cdc2 and cyclin B1 were ubiquitinated by GA. MG132 abrogated the GA-induced decrease of Cdc2 and cyclin B1 indicating that these proteins were degraded by proteasomes. In conclusion, GA controls the stability of Cdc2 and cyclin B1 in glioblastomas cell species-dependently. Cdc2 and cyclin B1 might be responsible for the different responses of glioblastoma cell lines to GA. |
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Authors:
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Naoko Nomura; Motohiro Nomura; Elizabeth W Newcomb; David Zagzag |
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Publication Detail:
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Type: Journal Article Date: 2007-01-21 |
Journal Detail:
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Title: Biochemical pharmacology Volume: 73 ISSN: 0006-2952 ISO Abbreviation: Biochem. Pharmacol. Publication Date: 2007 May |
Date Detail:
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Created Date: 2007-04-09 Completed Date: 2007-06-04 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0101032 Medline TA: Biochem Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 1528-36 Citation Subset: IM |
Affiliation:
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Department of Ophthalmology, Kanazawa Social Insurance Hospital, Kanazawa, Japan. nomura413jp@yahoo.co.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antibiotics, Antineoplastic
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pharmacology* Benzoquinones / pharmacology* CDC2 Protein Kinase / genetics, metabolism* Cell Cycle / drug effects Cell Proliferation / drug effects Cyclin B / genetics, metabolism* Cyclin B1 Down-Regulation / drug effects G2 Phase / drug effects*, physiology Glioblastoma / pathology* Half-Life Humans Lactams, Macrocyclic / pharmacology* Proteasome Endopeptidase Complex / metabolism, pharmacology Tumor Cells, Cultured Ubiquitin / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Antibiotics, Antineoplastic; 0/Benzoquinones; 0/CCNB1 protein, human; 0/Cyclin B; 0/Cyclin B1; 0/Lactams, Macrocyclic; 0/Ubiquitin; 30562-34-6/geldanamycin; EC 2.7.11.22/CDC2 Protein Kinase; EC 3.4.25.1/Proteasome Endopeptidase Complex |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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