| Ubiquitin-like protein MNSFβ covalently binds to Bcl-G and enhances lipopolysaccharide (LPS)/interferon γ (IFNγ)-induced apoptosis in macrophages. | |
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MedLine Citation:
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PMID: 23298187 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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MNSFβ is a ubiquitously expressed member of the ubiquitin-like family that has been involved in various biological functions. Previous studies have demonstrated that MNSFβ covalently binds to intracellular pro-apoptotic protein Bcl-G and regulates the ERK-MAPK cascade in mouse macrophage cell line, Raw264.7. In this study, we demonstrate that MNSFβ promotes lipopolysaccharide (LPS)/interferon γ (IFNγ)-induced apoptosis of Raw264.7 macrophages. In Raw264.7 cells treated with MNSFβ small interfering RNA (siRNA) LPS/IFNγ- or NO donor S-nitrosoglutathione (GSNO)- induced apoptosis was inhibited. SiRNA-mediated knockdown of MNSFβ did not affect iNOS expression in LPS/ IFNγ-stimulated Raw264.7 cells. Conversely, co-transfection with MNSFβ and Bcl-G greatly enhanced LPS/IFNγ- induced apoptosis in Raw264.7 cells, accompanied with an increased expression of p53 and a decreased Cox-2 activity. Unlike co-transfection with wild-type MNSFβ, co-transfection of a mutant MNSFβ (G74A) and Bcl-G did not result in an enhancement of LPS/IFNγ- induced apoptosis. Co-overexpression of MNSFβ and Bcl-G reduced GSNO-induced ERK1/2 phosphorylation. Furthermore, EMSA experiments revealed that MNSFβ down-regulates ERK/AP-1 signaling cascade leading to Cox-2 activation. We also observed that MNSFβ•Bcl-G promotes LPS/IFNγ-induced apoptosis of mouse peritoneal macrophages, together with a decrease in Cox-2 expression. Taken together, our data indicate an apoptosis enhancing effect of MNSFβ•Bcl-G is due in part to the down-regulation of Cox-2 activation in macrophages. © 2013 The Authors Journal compilation © 2013 FEBS. |
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Authors:
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Jun Watanabe; Mai Nakagawa; Natsuko Watanabe; Morihiko Nakamura |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-1-9 |
Journal Detail:
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Title: The FEBS journal Volume: - ISSN: 1742-4658 ISO Abbreviation: FEBS J. Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-9 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101229646 Medline TA: FEBS J Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2013 The Authors Journal compilation © 2013 FEBS. |
Affiliation:
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The Department of Cooperative Medical Research, Collaboration Center, Shimane University, Izumo, 693-8501, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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