About: Abstract Many studies have shown that the activation of β-catenin signaling can promote oncogenesis, and it is therefore of interest to find agents that modulate this pathway. Recent work has shown using B lymphoma cells that infection by Epstein–Barr virus (EBV) and expression of its latent membrane protein (LMP)-1, cause increases in the expression of β-catenin and cellular transformation. Conversely, results from cell-based small molecule screening studies have shown that the antibiotic hexachlorophene can down-regulate β-catenin in colon cancer cells. Here we report that hexachlorophene also counteracts the elevated β-catenin levels in EBV-infected B lymphomas. This is associated with restoration in levels of Siah-1 (an E3 ubiquitin ligase that is active in β-catenin regulation) which had been diminished by LMP-1. Our results suggest that Siah-1 is targeted by both LMP-1 and hexachlorophene with opposite effects. The hexachlorophene modulation of Siah-1 and β-catenin is independent of p53 and results in reduced expression of cyclin-D1 and c-Myc (target genes of β-catenin), leading to the growth arrest of B lymphoma cells. From these results we propose that hexachlorophene may provide a novel therapeutic strategy for EBV-infected B lymphoma cells by reducing β-catenin levels via the restoration of Siah-1.   Goto Sponge  NotDistinct  Permalink

An Entity of Type : fabio:Abstract, within Data Space : wasabi.inria.fr associated with source document(s)

AttributesValues
type
value
  • Abstract Many studies have shown that the activation of β-catenin signaling can promote oncogenesis, and it is therefore of interest to find agents that modulate this pathway. Recent work has shown using B lymphoma cells that infection by Epstein–Barr virus (EBV) and expression of its latent membrane protein (LMP)-1, cause increases in the expression of β-catenin and cellular transformation. Conversely, results from cell-based small molecule screening studies have shown that the antibiotic hexachlorophene can down-regulate β-catenin in colon cancer cells. Here we report that hexachlorophene also counteracts the elevated β-catenin levels in EBV-infected B lymphomas. This is associated with restoration in levels of Siah-1 (an E3 ubiquitin ligase that is active in β-catenin regulation) which had been diminished by LMP-1. Our results suggest that Siah-1 is targeted by both LMP-1 and hexachlorophene with opposite effects. The hexachlorophene modulation of Siah-1 and β-catenin is independent of p53 and results in reduced expression of cyclin-D1 and c-Myc (target genes of β-catenin), leading to the growth arrest of B lymphoma cells. From these results we propose that hexachlorophene may provide a novel therapeutic strategy for EBV-infected B lymphoma cells by reducing β-catenin levels via the restoration of Siah-1.
Subject
  • Virology
  • Signal transduction
  • Viral proteins
  • Programmed cell death
  • Oncogenes
  • Armadillo-repeat-containing proteins
  • Catenins
part of
is abstract of
is hasSource of
Faceted Search & Find service v1.13.91 as of Mar 24 2020


Alternative Linked Data Documents: Sponger | ODE     Content Formats:       RDF       ODATA       Microdata      About   
This material is Open Knowledge   W3C Semantic Web Technology [RDF Data]
OpenLink Virtuoso version 07.20.3229 as of Jul 10 2020, on Linux (x86_64-pc-linux-gnu), Single-Server Edition (94 GB total memory)
Data on this page belongs to its respective rights holders.
Virtuoso Faceted Browser Copyright © 2009-2024 OpenLink Software