Nucleotide oligomerization domain-2 interacts with 2′-5′-oligoadenylate synthetase type 2 and enhances RNase-L function in THP-1 cells

Jae W. Dugan, Amador Albor, Larry David, Jonathan Fowlkes, Marc T. Blackledge, Tammy M. Martin, Stephen R. Planck, Holly L. Rosenzweig, James T. Rosenbaum, Michael P. Davey

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Nucleotide-binding and oligomerization domain-2 (NOD2) is an intracellular protein involved in innate immunity and linked to chronic inflammatory diseases in humans. Further characterization of the full spectrum of proteins capable of binding to NOD2 may provide new insights into its normal functioning as well as the mechanisms by which mutated forms cause disease. Using a proteomics approach to study human THP-1 cells, we have identified 2′-5′-oligoadenylate synthetase type 2 (OAS2), a dsRNA binding protein involved in the pathway that activates RNase-L, as a new binding partner for NOD2. The interaction was confirmed using over-expression of OAS2 and NOD2 in HEK cells. Further confirmation was obtained by detecting NOD2 in immunoprecipitates of endogenous OAS2 in THP-1 cells. Finally, over-expression of NOD2 in THP-1 cells led to enhanced RNase-L activity in cells treated with poly(I:C), a mimic of double-stranded RNA virus infection. These data indicate connectivity in pathways involved in innate immunity to bacteria and viruses and suggest a regulatory role whereby NOD2 enhances the function of RNase-L.

Original languageEnglish (US)
Pages (from-to)560-566
Number of pages7
JournalMolecular Immunology
Volume47
Issue number2-3
DOIs
StatePublished - Dec 1 2009

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Keywords

  • 2′-5′-Oligoadenylate synthetase type 2
  • Innate immunity
  • Nucleotide-binding and oligomerization domain-2
  • Proteomics
  • RNase-L

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

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