PRL-3 activates NF-κB signaling pathway by interacting with RAP1

Biochem Biophys Res Commun. 2013 Jan 4;430(1):196-201. doi: 10.1016/j.bbrc.2012.11.036. Epub 2012 Nov 21.

Abstract

Phosphatase of regenerating liver (PRL-3) promotes cancer metastasis through enhanced cell motility and invasiveness, however its role in tumorigenesis remains unclear. Herein, we reported that PRL-3 interacts with telomere-related protein RAP1. PRL-3 promotes the cytosolic localization of RAP1, which is counteracted by silencing of PRL-3. Immunohistochemical staining of colon cancer tissue array (n=170) revealed that high level of PRL-3 associates with cytosolic localization of RAP1 (p=0.01). Microarray analysis showed that PRL-3 regulates expression of diverse genes and enhances phosphorylation of p65 subunit of NF-κB in a RAP1-dependent manner. Furthermore, PRL-3 transcriptionally activates RAP1 expression, which is counteracted by ablating p65. Therefore, our results demonstrate PRL-3 as a novel regulator of NF-κB signaling pathway through RAP1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cytosol / metabolism
  • Gene Expression Regulation
  • Humans
  • NF-kappa B / metabolism*
  • Neoplasm Proteins / metabolism*
  • Phosphorylation
  • Protein Tyrosine Phosphatases / metabolism*
  • Shelterin Complex
  • Signal Transduction
  • Telomere-Binding Proteins / metabolism*
  • Transcription Factor RelA / metabolism

Substances

  • NF-kappa B
  • Neoplasm Proteins
  • Shelterin Complex
  • TERF2IP protein, human
  • Telomere-Binding Proteins
  • Transcription Factor RelA
  • PTP4A3 protein, human
  • Protein Tyrosine Phosphatases