AIG1 is a novel Pirh2-interacting protein that activates the NFAT signaling pathway

Front Biosci (Elite Ed). 2011 Jun 1;3:834-42.

Abstract

Pirh2 is an E3 ligase that negatively regulates p53 through both direct physical interaction and ubiquitin-mediated proteolysis. Here, we identified a novel Pirh2-interacting protein, AIG1, by yeast two-hybrid screening and confirmed its interaction with p53 both in vitro and in vivo. Quantitative real-time reverse transcription-PCR analysis showed that AIG1 expression levels were reduced in 50 out of 79 (63%) human hepatocellular carcinomas (HCCs) when compared to matched, non-cancerous liver tissue; levels were significantly different between HCCs with or without lymph node metastasis. Kaplan-Meier analysis indicated that the survival time of HCC patients down-regulated for AIG1 is much shorter than it is for patients up-regulated for AIG1 expression (p = 0.0313 as determined by the Log-rank test). Finally, AIG1 activated the nuclear factor of activated T cells (NFAT) signaling pathway in a dose-dependent manner when over-expressed in HEK293T cells. Our results suggest AIG1 could serve as a new biomarker for the diagnosis and prognostic evaluation of HCCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Line
  • DNA Primers
  • Female
  • Humans
  • Male
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology*
  • Middle Aged
  • Molecular Sequence Data
  • NFATC Transcription Factors / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Signal Transduction / physiology*
  • Subcellular Fractions / metabolism
  • Two-Hybrid System Techniques
  • Ubiquitin-Protein Ligases / chemistry
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitin-Protein Ligases / physiology*
  • Ubiquitination

Substances

  • AIG1 protein, human
  • DNA Primers
  • Membrane Proteins
  • NFATC Transcription Factors
  • RCHY1 protein, human
  • Ubiquitin-Protein Ligases