CHIP facilitates ubiquitination of inducible nitric oxide synthase and promotes its proteasomal degradation

Cell Immunol. 2009;258(1):38-43. doi: 10.1016/j.cellimm.2009.03.009. Epub 2009 Apr 10.


Inducible nitric oxide synthase (iNOS) is responsible for nitric oxide (NO) synthesis from l-arginine in response to inflammatory mediators. It is reported that iNOS is degraded mainly by the ubiquitin-proteasome pathway in RAW264.7 cells and human embryonic kidney (HEK) 293 cells. In this study, we showed that iNOS was ubiquitinated and degraded dependent on CHIP (COOH terminus of heat shock protein 70-interacting protein), a chaperone-dependent ubiquitin ligase. The results from overexpression and RNAi experiments demonstrated that CHIP decreased the protein level of iNOS, shortened the half-life of iNOS and attenuated the production of NO. Furthermore, CHIP promoted ubiquitination and proteasomal degradation of iNOS by associating with iNOS. These results suggest that CHIP plays an important role in regulation iNOS activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Humans
  • Mice
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase Type II / metabolism*
  • Plasmids
  • Proteasome Endopeptidase Complex / metabolism*
  • Transfection
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitination / physiology*


  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • STUB1 protein, human
  • Ubiquitin-Protein Ligases
  • Proteasome Endopeptidase Complex