The role of the proteasome-ubiquitin pathway in regulation of the IFN-gamma mediated anti-VSV response in neurons.
Pharmacologic inhibition of the proteasome resulted in increased NOS-1 protein levels and increased NO production by neuronal cells. This correlated with an increased antiviral effect of IFN-gamma against the replication of vesicular stomatitis virus (VSV) replication in vitro. We also observed that a regulatory protein, Protein Inhibitor of NOS-1 (PIN) was down-regulated by IFN-gamma treatment, and more ubiquitinated PIN accumulated in IFN-gamma treated neurons. In cells of the reticuloendothelial system, IFN-gamma treatment induces the expression of a set of low molecular weight MHC-encoded proteins (LMPs), which replace the beta-subunit of the proteasome complex during the proteasome neosynthesis, resulting in a complex termed the immunoproteasome. LMP2, -7, and -10 were induced and the immunoproteasome was generated by IFN-gamma treatment in neuronal cells. Importantly, we observed that IFN-gamma induced inhibition of VSV protein synthesis was not dependent on ubiquitination.
Yang
Jingjun
J
Department of Biology, New York University, New York, NY 10003, USA.
Tugal
Derin
D
Reiss
Carol Shoshkes
CS
D000818:Animals; D000998:Antiviral Agents / Q000276:immunology* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004398:Dyneins / Q000378:metabolism; D005347:Fibroblasts; D007371:Interferon-gamma / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000201:enzymology / Q000821:virology*; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors; D012333:RNA, Messenger / Q000378:metabolism; D018353:Rhabdoviridae Infections / Q000276:immunology* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000276:immunology; D025801:Ubiquitin / Q000378:metabolism*; D014721:Vesicular stomatitis Indiana virus / Q000254:growth & development / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology
D000998:Antiviral Agents; D061988:Proteasome Inhibitors; D012333:RNA, Messenger; D025801:Ubiquitin; D007371:Interferon-gamma; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D046988:Proteasome Endopeptidase Complex; D004398:Dyneins