Regulation of Nod1-mediated signaling pathways

Cell Death Differ. 2007 Apr;14(4):830-9. doi: 10.1038/sj.cdd.4402070. Epub 2006 Dec 22.


Nod1 is a member of the NLR/Nod/CATERPILLER family. It acts as a sensor for intracellular bacteria by recognizing specific glycopeptides derived from peptidoglycan. Nod1 activation mediates distinct cellular responses including activation of MAP kinases, IL-8 release, apoptosis and suppression of several estrogen-dependent responses in MCF-7 cells. Here we have extended these studies by identifying key regulatory steps in Nod1-dependent signaling pathways. We provide multiple lines of data showing that Nod1-dependent apoptosis is a caspase 8-mediated event and that apoptosis requires RIP2. In contrast, several lines of evidence show that Nod1-dependent JNK activation and IL-8 production did not require the presence of caspase 8 but required activation of TAK1 as well as RIP2. Thus, we have identified several key control points that lie downstream of Nod1. This work provides the basis for further studies of the biological significance and regulation of the Nod1 pathway.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Caspase 8 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Humans
  • Interleukin-8 / biosynthesis
  • Intracellular Signaling Peptides and Proteins / metabolism
  • MAP Kinase Kinase Kinases / metabolism
  • Mutagenesis, Site-Directed
  • Nod1 Signaling Adaptor Protein / metabolism*
  • Nod2 Signaling Adaptor Protein / metabolism*
  • Protein Interaction Mapping
  • Receptor-Interacting Protein Serine-Threonine Kinase 2 / metabolism
  • Signal Transduction / physiology
  • Tumor Cells, Cultured


  • Interleukin-8
  • Intracellular Signaling Peptides and Proteins
  • Nod1 Signaling Adaptor Protein
  • Nod2 Signaling Adaptor Protein
  • Receptor-Interacting Protein Serine-Threonine Kinase 2
  • MAP Kinase Kinase Kinases
  • MAP kinase kinase kinase 7
  • Caspase 8