BCL6 suppression of BCL2 via Miz1 and its disruption in diffuse large B cell lymphoma Academic Article uri icon

Overview

MeSH Major

  • DNA-Binding Proteins
  • Lymphoma, Large B-Cell, Diffuse
  • Protein Inhibitors of Activated STAT
  • Proto-Oncogene Proteins c-bcl-2

abstract

  • The BCL6 proto-oncogene encodes a transcriptional repressor that is required for germinal center (GC) formation and whose deregulation by genomic lesions is implicated in the pathogenesis of GC-derived diffuse large B cell lymphoma (DLBCL) and, less frequently, follicular lymphoma (FL). The biological function of BCL6 is only partially understood because no more than a few genes have been functionally characterized as direct targets of BCL6 transrepression activity. Here we report that the anti-apoptotic proto-oncogene BCL2 is a direct target of BCL6 in GC B cells. BCL6 binds to the BCL2 promoter region by interacting with the transcriptional activator Miz1 and suppresses Miz1-induced activation of BCL2 expression. BCL6-mediated suppression of BCL2 is lost in FL and DLBCL, where the 2 proteins are pathologically coexpressed, because of BCL2 chromosomal translocations and other mechanisms, including Miz1 deregulation and somatic mutations in the BCL2 promoter region. These results identify an important function for BCL6 in facilitating apoptosis of GC B cells via suppression of BCL2, and suggest that blocking this pathway is critical for lymphomagenesis.

publication date

  • July 7, 2009

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2708681

Digital Object Identifier (DOI)

  • 10.1073/pnas.0903854106

PubMed ID

  • 19549844

Additional Document Info

start page

  • 11294

end page

  • 9

volume

  • 106

number

  • 27