KSHV LANA inhibits TGF-beta signaling through epigenetic silencing of the TGF-beta type II receptor. Academic Article uri icon

Overview

abstract

  • Signaling through the transforming growth factor-beta (TGF-beta) pathway results in growth inhibition and induction of apoptosis in various cell types. We show that this pathway is blocked in Kaposi sarcoma herpesvirus (KSHV)-infected primary effusion lymphoma through down-regulation of the TGF-beta type II receptor (TbetaRII) by epigenetic mechanisms. Our data also suggest that KSHV infection may result in lower expression of TbetaRII in Kaposi sarcoma and multicentric Castleman disease. KSHV-encoded LANA associates with the promoter of TbetaRII and leads to its methylation and to the deacetylation of proximal histones. Reestablishment of signaling through this pathway reduces viability of these cells, inferring that KSHV-mediated blockage of TGF-beta signaling plays a role in the establishment and progression of KSHV-associated neoplasia. These data suggest a mechanism whereby KSHV evades both the antiproliferative effects of TGF-beta signaling by silencing TbetaRII gene expression and immune recognition by suppressing TGF-beta-responsive immune cells through the elevated secretion of TGF-beta1.

publication date

  • January 16, 2008

Research

keywords

  • Antigens, Viral
  • Epigenesis, Genetic
  • Herpesvirus 8, Human
  • Nuclear Proteins
  • Protein Serine-Threonine Kinases
  • Receptors, Transforming Growth Factor beta
  • Signal Transduction
  • Transforming Growth Factor beta

Identity

PubMed Central ID

  • PMC2343603

Scopus Document Identifier

  • 44649172694

Digital Object Identifier (DOI)

  • 10.1182/blood-2007-09-110544

PubMed ID

  • 18199825

Additional Document Info

volume

  • 111

issue

  • 9