| Glycogen synthase kinase-3 and Omi/HtrA2 induce annexin A2 cleavage followed by cell cycle inhibition and apoptosis. | |
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MedLine Citation:
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PMID: 19656851 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Annexin A2 is involved in multiple cellular processes, including cell survival, growth, division, and differentiation. A lack of annexin A2 makes cells more sensitive to apoptotic stimuli. Here, we demonstrate a potential mechanism for apoptotic stimuli-induced annexin A2 cleavage, which contributes to cell cycle inhibition and apoptosis. Annexin A2 was persistently expressed around the proliferative but not the necrotic region in BALB/c nude mice with human lung epithelial carcinoma cell A549-derived tumors. Knockdown expression of annexin A2 made cells susceptible to either serum withdrawal-induced cell cycle inhibition or cisplatin-induced apoptosis. Under apoptotic stimuli, annexin A2 was time-dependently cleaved. Mechanistic studies have shown that protein phosphatase 2A (PP2A)-activated glycogen synthase kinase (GSK)-3 is essential for this process. Therefore, inhibiting GSK-3 reversed serum withdrawal-induced cell cycle inhibition and cisplatin-induced apoptosis. Furthermore, inhibiting serine proteases blocked apoptotic stimuli-induced annexin A2 cleavage. Bax activation and Mcl-1 destabilization, which is regulated by PP2A and GSK-3, caused annexin A2 cleavage via an Omi/HtrA2-dependent pathway. Taking these results together, we conclude that GSK-3 and Omi/HtrA2 synergistically cause annexin A2 cleavage and then cell cycle inhibition or apoptosis. |
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Authors:
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Chi-Yun Wang; Yee-Shin Lin; Wu-Chou Su; Chia-Ling Chen; Chiou-Feng Lin |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-08-05 |
Journal Detail:
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Title: Molecular biology of the cell Volume: 20 ISSN: 1939-4586 ISO Abbreviation: Mol. Biol. Cell Publication Date: 2009 Oct |
Date Detail:
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Created Date: 2009-10-01 Completed Date: 2010-02-08 Revised Date: 2010-09-24 |
Medline Journal Info:
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Nlm Unique ID: 9201390 Medline TA: Mol Biol Cell Country: United States |
Other Details:
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Languages: eng Pagination: 4153-61 Citation Subset: IM |
Affiliation:
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Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Annexin A2 / genetics, metabolism* Antineoplastic Agents / pharmacology Apoptosis / drug effects, physiology* Blotting, Western Cell Cycle / drug effects, physiology* Cell Line, Tumor Cisplatin / pharmacology Culture Media, Serum-Free / pharmacology Glycogen Synthase Kinase 3 / genetics, metabolism* Green Fluorescent Proteins / genetics, metabolism Humans Membrane Potential, Mitochondrial / drug effects Mice Mice, Inbred BALB C Mice, Nude Mitochondrial Proteins / genetics, metabolism* Mutation Neoplasms, Experimental / genetics, metabolism, pathology Protein Phosphatase 2 / metabolism RNA Interference Reverse Transcriptase Polymerase Chain Reaction Serine Endopeptidases / genetics, metabolism* Transplantation, Heterologous bcl-2-Associated X Protein / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Annexin A2; 0/Antineoplastic Agents; 0/Culture Media, Serum-Free; 0/Mitochondrial Proteins; 0/bcl-2-Associated X Protein; 147336-22-9/Green Fluorescent Proteins; 15663-27-1/Cisplatin; EC 2.7.11.26/Glycogen Synthase Kinase 3; EC 3.1.3.16/Protein Phosphatase 2; EC 3.4.21.-/Omi serine protease; EC 3.4.21.-/Serine Endopeptidases |
| Comments/Corrections | |
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