PRMT5 interacts with the BCL6 oncoprotein and is required for germinal center formation and lymphoma cell survival. Academic Article uri icon

Overview

abstract

  • The germinal center (GC) reaction plays an important role in generating humoral immunity and is believed to give rise to most B-cell lymphomas. GC entry and exit are tightly regulated processes, controlled by the actions of transcription factors such as BCL6. Herein, we demonstrate that protein arginine methyltransferase 5 (PRMT5), a symmetric dimethyl arginine methyltransferase, is also necessary for GC formation and affinity maturation. PRMT5 contributes to GC formation and affinity maturation at least in part through its direct interaction with and methylation of BCL6 at arginine 305 (R305), a modification necessary for the full transcriptional repressive effects of BCL6. Inhibition of PRMT5 in B-cell lymphoma lines led to significant upregulation of BCL6 target genes, and the concomitant inhibition of both BCL6 and PRMT5 exhibited synergistic killing of BCL6-expressing lymphoma cells. Our studies identify PRMT5 as a novel regulator of the GC reaction and highlight the mechanistic rationale of cotargeting PRMT5 and BCL6 in lymphoma.

publication date

  • August 6, 2018

Research

keywords

  • Germinal Center
  • Lymphoma
  • Protein Interaction Maps
  • Protein-Arginine N-Methyltransferases
  • Proto-Oncogene Proteins c-bcl-6

Identity

PubMed Central ID

  • PMC6236466

Scopus Document Identifier

  • 85056265822

Digital Object Identifier (DOI)

  • 10.1182/blood-2018-02-831438

PubMed ID

  • 30082494

Additional Document Info

volume

  • 132

issue

  • 19