Document Detail

Ubiquitin-like protein MNSFβ covalently binds to Bcl-G and enhances lipopolysaccharide (LPS)/interferon γ (IFNγ)-induced apoptosis in macrophages.
MedLine Citation:
PMID:  23298187     Owner:  NLM     Status:  Publisher    
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.
Jun Watanabe; Mai Nakagawa; Natsuko Watanabe; Morihiko Nakamura
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-9
Journal Detail:
Title:  The FEBS journal     Volume:  -     ISSN:  1742-4658     ISO Abbreviation:  FEBS J.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101229646     Medline TA:  FEBS J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2013 The Authors Journal compilation © 2013 FEBS.
The Department of Cooperative Medical Research, Collaboration Center, Shimane University, Izumo, 693-8501, Japan.
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