| ABC50 modulates sensitivity of HL60 leukemic cells to endoplasmic reticulum (ER) stress-induced cell death. | |
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MedLine Citation:
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PMID: 21087599 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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ABC50 (aka ABCF1) is a member of the ATP Binding Cassette protein family. ABC50 stimulates complex formation between eIF2, GTP and Met-tRNA implicating it in translation initiation. Econazole (Ec) is an imidazole anti-fungal that induces endoplasmic reticulum (ER) stress in mammalian cells by promoting ER Ca(2+) depletion and sustained protein synthesis inhibition. HL60 cells selected for Ec resistance were found to exhibit a multi-drug resistance phenotype associated specifically with ER stress. Differential Display was used to identify ABC50 as an overexpressed gene in resistant cells. ABC50 knockdown (KD) in Ec-resistant HL60 cells partially restored Ec sensitivity. In parental HL60 cells, ABC50 KD increased sensitivity to Ec, thapsigargin and tunicamycin but not to serum withdrawal or etoposide. ABC50 overexpression (OE) partially and specifically decreased sensitivity to ER stress agents. ABC50 KD or OE had no effect on ROS generation by Ec, ER Ca(2+) stores or thapsigargin-stimulated influx. Increased eIF2α phosphorylation in response to ER stress was observed in the KD cells while decreased phosphorylation was observed in the OE cells. Ribosomal content was reduced in ABC50 KD cells and increased in OE cells. Knockdown suppressed protein synthesis while OE increased it. Protein synthesis was sustained in ABC50 OE cells exposed to Ec. ABC50 OE promoted ER stress resistance and increased antibody production in the hybridoma GK1.5 suggesting it may be useful for the overproduction of specific proteins. Taken together, these results indicate that ABC50 modulates sensitivity to Ec and other ER stress agents primarily through its effects on protein synthesis. |
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Authors:
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Yongmao Yu; Yicheng Zhang; Ziping Zhu; Stuart A Berger |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-11-16 |
Journal Detail:
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Title: Biochemical pharmacology Volume: 81 ISSN: 1873-2968 ISO Abbreviation: Biochem. Pharmacol. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-17 Completed Date: - Revised Date: - |
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: 488-97 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Arthritis and Immune Disorder Research Centre, TGRI, University Health Network, Canada. |
Export Citation:
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Descriptor/Qualifier:
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| Grant Support | |
ID/Acronym/Agency:
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//Canadian Institutes of Health Research |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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