BCL6 represses Smad signaling in transforming growth factor-beta resistance

Cancer Res. 2008 Feb 1;68(3):783-9. doi: 10.1158/0008-5472.CAN-07-0008.


Transforming growth factor-beta (TGF-beta) controls a wide spectrum of cellular processes. Deregulation of TGF-beta signaling contributes to the pathogenesis of many diseases including cancer and autoimmune diseases. TGF-beta signaling is generally mediated through intracellular signal transducers and transcription factors called Smads. Herein, we have identified the oncoprotein BCL6 as a transcriptional corepressor of tumor suppressor Smad4. BCL6 physically interacts with Smad3 and Smad4, disrupts the Smad-p300 interaction, and represses the transcriptional activity of Smad4. In accordance, B-cell lymphoma cells with a high expression level of BCL6 were found to be refractory to TGF-beta antiproliferative response, whereas knockdown of BCL6 expression in B-cell lymphoma cells partially restores the TGF-beta responses. This study provides strong evidence that overexpression of BCL6 contributes to TGF-beta resistance in B-cell lymphoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Burkitt Lymphoma / drug therapy
  • Burkitt Lymphoma / genetics
  • Burkitt Lymphoma / metabolism*
  • Burkitt Lymphoma / pathology
  • Cell Growth Processes / drug effects
  • Cell Growth Processes / physiology
  • Cell Line, Tumor
  • Chromatin / metabolism
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • E1A-Associated p300 Protein / metabolism
  • Humans
  • Lymphoma, B-Cell / drug therapy
  • Lymphoma, B-Cell / genetics
  • Lymphoma, B-Cell / metabolism*
  • Lymphoma, B-Cell / pathology
  • Proto-Oncogene Proteins c-bcl-6
  • RNA, Small Interfering / genetics
  • Rats
  • Signal Transduction
  • Smad4 Protein / genetics
  • Smad4 Protein / metabolism*
  • Transcription, Genetic
  • Transforming Growth Factor beta / antagonists & inhibitors
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / pharmacology*


  • BCL6 protein, human
  • Chromatin
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins c-bcl-6
  • RNA, Small Interfering
  • SMAD4 protein, human
  • Smad4 Protein
  • Transforming Growth Factor beta
  • E1A-Associated p300 Protein
  • EP300 protein, human