PSMA7 directly interacts with NOD1 and regulates its function

Cell Physiol Biochem. 2013;31(6):952-9. doi: 10.1159/000350113. Epub 2013 Jun 26.

Abstract

Background/aims: Recent reports showed that proteasome subunit alpha type-7 (PSMA7) was overexpressed in colorectal cancer. To investigate the mechanism of PSMA7 in promotion of colorectal cancer, we screened for its interaction partners.

Methods and results: This study found that PSMA7 associated with nucleotide-binding oligomerization domain-containing protein 1 (NOD1) by yeast two-hybrid screening, co-immunoprecipitation (IP), and GST-pull down assay. As shown by Western blotting and ubiquitin assay, PSMA7 downregulated the expression of NOD1 in a proteasome-dependent manner. Overexpression of PSMA7 in HCT116 cells resulted in an inhibition of NOD1-mediated apoptosis and NF-κB activation, whereas knockdown of PSMA7 by RNA interference enhanced NOD1 activity.

Conclusion: Our data suggest that PSMA7 is a negative regulator of the NOD1, and may promote tumor growth by its inhibitory role on NOD1.

MeSH terms

  • Apoptosis
  • Down-Regulation
  • HCT116 Cells
  • HEK293 Cells
  • Humans
  • NF-kappa B / metabolism
  • Nod1 Signaling Adaptor Protein / genetics
  • Nod1 Signaling Adaptor Protein / metabolism*
  • Proteasome Endopeptidase Complex / chemistry
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / metabolism*
  • Protein Binding
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Transfection
  • Two-Hybrid System Techniques
  • Ubiquitination

Substances

  • NF-kappa B
  • NOD1 protein, human
  • Nod1 Signaling Adaptor Protein
  • RNA, Small Interfering
  • PSMA7 protein, human
  • Proteasome Endopeptidase Complex