Document Detail


Geldanamycin induces G2 arrest in U87MG glioblastoma cells through downregulation of Cdc2 and cyclin B1.
MedLine Citation:
PMID:  17324379     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Naoko Nomura; Motohiro Nomura; Elizabeth W Newcomb; David Zagzag
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Publication Detail:
Type:  Journal Article     Date:  2007-01-21
Journal Detail:
Title:  Biochemical pharmacology     Volume:  73     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  2007 May 
Date Detail:
Created Date:  2007-04-09     Completed Date:  2007-06-04     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1528-36     Citation Subset:  IM    
Affiliation:
Department of Ophthalmology, Kanazawa Social Insurance Hospital, Kanazawa, Japan. nomura413jp@yahoo.co.jp
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MeSH Terms
Descriptor/Qualifier:
Antibiotics, Antineoplastic / 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:
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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