PRMT5 interacts with the BCL6 oncoprotein and is required for germinal center formation and lymphoma cell survival

Xiaoqing Lu, Tharu M. Fernando, Chen Lossos, Nevin Yusufova, Fan Liu, Lorena Fontán, Matthew Durant, Huimin Geng, Jacob Melnick, Yuan Luo, Francisco Vega, Vincent T. Moy, Giorgio Inghirami, Stephen D Nimer, Ari M. Melnick, Izidore Lossos

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2026-2039
Number of pages14
JournalBlood
Volume132
Issue number19
DOIs
StatePublished - Nov 8 2018

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Protein-Arginine N-Methyltransferases
Germinal Center
Oncogene Proteins
Lymphoma
Cell Survival
Cells
B-Cell Lymphoma
Methylation
Humoral Immunity
Arginine
Transcription Factors
Up-Regulation
Genes
Cell Line

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

PRMT5 interacts with the BCL6 oncoprotein and is required for germinal center formation and lymphoma cell survival. / Lu, Xiaoqing; Fernando, Tharu M.; Lossos, Chen; Yusufova, Nevin; Liu, Fan; Fontán, Lorena; Durant, Matthew; Geng, Huimin; Melnick, Jacob; Luo, Yuan; Vega, Francisco; Moy, Vincent T.; Inghirami, Giorgio; Nimer, Stephen D; Melnick, Ari M.; Lossos, Izidore.

In: Blood, Vol. 132, No. 19, 08.11.2018, p. 2026-2039.

Research output: Contribution to journalArticle

Lu, X, Fernando, TM, Lossos, C, Yusufova, N, Liu, F, Fontán, L, Durant, M, Geng, H, Melnick, J, Luo, Y, Vega, F, Moy, VT, Inghirami, G, Nimer, SD, Melnick, AM & Lossos, I 2018, 'PRMT5 interacts with the BCL6 oncoprotein and is required for germinal center formation and lymphoma cell survival', Blood, vol. 132, no. 19, pp. 2026-2039. https://doi.org/10.1182/blood-2018-02-831438
Lu, Xiaoqing ; Fernando, Tharu M. ; Lossos, Chen ; Yusufova, Nevin ; Liu, Fan ; Fontán, Lorena ; Durant, Matthew ; Geng, Huimin ; Melnick, Jacob ; Luo, Yuan ; Vega, Francisco ; Moy, Vincent T. ; Inghirami, Giorgio ; Nimer, Stephen D ; Melnick, Ari M. ; Lossos, Izidore. / PRMT5 interacts with the BCL6 oncoprotein and is required for germinal center formation and lymphoma cell survival. In: Blood. 2018 ; Vol. 132, No. 19. pp. 2026-2039.
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