title: AIG1 is a novel Pirh2-interacting protein that activates the NFAT signaling pathway.
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.
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wu
authors.forename: Meiqian
authors.initials: M
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Keke
authors.initials: K
authors.lastname: Huo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D008875:Middle Aged; D008969:Molecular Sequence Data; D050778:NFATC Transcription Factors / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology*; D013347:Subcellular Fractions / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D054875:Ubiquitination
chemical_list: C430102:AIG1 protein, human; D017931:DNA Primers; D008565:Membrane Proteins; D050778:NFATC Transcription Factors; C485369:RCHY1 protein, human; D044767:Ubiquitin-Protein Ligases