RIPK2 NODs to XIAP and IBD

Semin Cell Dev Biol. 2021 Jan:109:144-150. doi: 10.1016/j.semcdb.2020.07.001. Epub 2020 Jul 3.

Abstract

The receptor-interacting protein kinases (RIPKs) are key regulators of inflammatory signalling and cell death pathways triggered by innate immune receptors, and RIPKs have emerged as promising therapeutic targets for treatment of immune-related disorders. RIPK2 mediates signalling responses initiated by the bacterial-sensing pattern recognition receptors nucleotide-binding oligomerization domain-containing proteins 1 and 2 (NOD1/2), which play a key role in regulation of intestinal immunity and inflammation. Modification of RIPK2 by non-degradative ubiquitin chains generated by the E3 ubiquitin ligase XIAP and other ligases govern NOD1/2 signalling. Recent advances suggest that the interaction between RIPK2 and XIAP is a druggable protein-protein interaction to modulate NOD1/2-dependent immune responses. Here, we discuss the mechanistic function of RIPK2 in immune signalling, its clinical relevance, and the on-going efforts to target RIPK2 in inflammatory bowel disease and beyond.

Keywords: Blau syndrome; Inflammatory bowel disease; NOD1; NOD2; RIPK2; Therapeutic target; Ubiquitin signalling; XIAP.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Humans
  • Inflammatory Bowel Diseases / genetics*
  • Inflammatory Bowel Diseases / pathology
  • Nod1 Signaling Adaptor Protein / metabolism*
  • Receptor-Interacting Protein Serine-Threonine Kinase 2 / metabolism*
  • X-Linked Inhibitor of Apoptosis Protein / metabolism*

Substances

  • NOD1 protein, human
  • Nod1 Signaling Adaptor Protein
  • X-Linked Inhibitor of Apoptosis Protein
  • XIAP protein, human
  • RIPK2 protein, human
  • Receptor-Interacting Protein Serine-Threonine Kinase 2