Abstract
UBP43 (also known as USP18) plays a role in the negative regulation of interferon-α/β signaling, and bone marrow cells in Ubp43-deficient mice exhibited hypersensitivity to interferon-α/β-mediated apoptosis. Here, we show that the mitochondrial apoptotic pathway and reactive oxygen species are major contributors to the elevated interferon-α/β-mediated apoptosis in Ubp43-deficient mouse bone marrow cells and in UBP43-knockdown THP-1 cells. Furthermore, TRAIL and FASL, which were proposed as apoptosis inducers upon interferon-α/β treatment in UBP43-knockdown adherent cancer cells, did not cause apoptosis in these hematopoietic cells. Therefore, although UBP43 depletion can cause hypersensitivity to interferon-α/β-mediated apoptosis in a broad range of cell types, the downstream pathway may vary depending on the cell type.
Copyright © 2012 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / drug effects
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Apoptosis / immunology*
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Caspase 3 / metabolism
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Cell Line
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Cell Line, Tumor
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Endopeptidases / genetics
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Endopeptidases / metabolism*
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Fas Ligand Protein / metabolism
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Gene Knockdown Techniques
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Hematopoietic Stem Cells / drug effects
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Hematopoietic Stem Cells / enzymology
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Hematopoietic Stem Cells / physiology*
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Humans
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Interferon-alpha / immunology*
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Interferon-alpha / pharmacology
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Interferon-beta / immunology*
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Interferon-beta / pharmacology
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Metabolic Networks and Pathways
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Mice
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Mitochondria / enzymology
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Mitochondria / metabolism*
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Reactive Oxygen Species / metabolism*
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TNF-Related Apoptosis-Inducing Ligand / metabolism
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Ubiquitin Thiolesterase
Substances
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Fas Ligand Protein
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Interferon-alpha
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Reactive Oxygen Species
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TNF-Related Apoptosis-Inducing Ligand
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Interferon-beta
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Endopeptidases
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Usp18 protein, mouse
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USP18 protein, human
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Ubiquitin Thiolesterase
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Caspase 3