PIN: A novel protein involved in IFN-γ accumulation of NOS-1 in neurons

Jingjun Yang, Natalie Nicole Dennison, Carol Shoshkes Reiss

Research output: Contribution to journalArticle

Abstract

In this study we investigate the role of the protein inhibitor of NOS-1 (PIN) in the interferon-γ (IFN-γ)-mediated posttranscriptional accumulation of nitric oxide synthase-1 (NOS-1) and the anti-vesicular stomatitis virus response in neuronal cells. IFN-γ-induced enhancement of NOS-1 activity is crucial for its antiviral activity in the central nervous system. IFN-γ treatment of neuronal cells results in an increase of total NOS-1 and decrease of total PIN proteins without alteration in their respective mRNA levels. PIN/NOS-1 complexes decreased after IFN-γ treatment. Transfection of cells with small interfering RNA (siRNA) for PIN results in a higher constitutive activity of NOS-1 and inhibition of viral replication. IFN-γ treatment did not change the amount of NOS-1 detectable by Western blot, when PIN is diminished by RNAi treatment. Overexpression of PIN results in lower constitutive NOS-1 expression and activity, and diminishes activation of NOS-1 by IFN-γ. Our findings indicate that in neurons, IFN-γ upregulates NOS-1 through proteasomal degradation of PIN.

Original languageEnglish (US)
Pages (from-to)9-17
Number of pages9
JournalDNA and cell biology
Volume27
Issue number1
DOIs
StatePublished - Jan 1 2008

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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