Nucleotide oligomerization domain-2 interacts with 2'-5'-oligoadenylate synthetase type 2 and enhances RNase-L function in THP-1 cells.
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.
Department of Veterans Affairs Medical Center, Portland, OR 97239-2999, USA.
Jae W
JW
Dugan
Amador
A
Albor
Larry
L
David
Jonathan
J
Fowlkes
Marc T
MT
Blackledge
Tammy M
TM
Martin
Stephen R
SR
Planck
Holly L
HL
Rosenzweig
James T
JT
Rosenbaum
Michael P
MP
Davey
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism*; D002460:Cell Line; D004722:Endoribonucleases / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology*; D053473:Nod2 Signaling Adaptor Protein / Q000378:metabolism*; D011070:Poly I-C / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D040901:Proteomics; D015203:Reproducibility of Results; D014161:Transduction, Genetic
C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D015088:2',5'-Oligoadenylate Synthetase; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease; D011070:Poly I-C