Glycolytic rate and lymphomagenesis depend on PARP14, an ADP ribosyltransferase of the B aggressive lymphoma (BAL) family.

Cho SH, Ahn AK, Bhargava P, Lee CH, Eischen CM, McGuinness O, Boothby M
Proc Natl Acad Sci U S A. 2011 108 (38): 15972-7

PMID: 21911376 · PMCID: PMC3179111 · DOI:10.1073/pnas.1017082108

Poly(ADP-ribose)polymerase (PARP)14--a member of the B aggressive lymphoma (BAL) family of macrodomain-containing PARPs--is an ADP ribosyltransferase that interacts with Stat6, enhances induction of certain genes by IL-4, and is expressed in B lymphocytes. We now show that IL-4 enhancement of glycolysis in B cells requires PARP14 and that this process is central to a role of PARP14 in IL-4-induced survival. Thus, enhancements of AMP-activated protein kinase activity restored both IL-4-induced glycolytic activity in Parp14(-/-) B cells and prosurvival signaling by this cytokine. Suppression of apoptosis is central to B-lymphoid oncogenesis, and elevated macro-PARP expression has been correlated with lymphoma aggressiveness. Strikingly, PARP14 deficiency delayed B lymphomagenesis and reversed the block to B-cell maturation driven by the Myc oncogene. Collectively, these findings reveal links between a mammalian ADP ribosyltransferase, cytokine-regulated metabolic activity, and apoptosis; show that PARP14 influences Myc-induced oncogenesis; and suggest that the PARP14-dependent capacity to increase cellular metabolic rates may be an important determinant of lymphoma pathobiology.

MeSH Terms (24)

AMP-Activated Protein Kinases Animals Apoptosis B-Lymphocytes Biological Transport Cells, Cultured Enzyme Activation Female Glucose Glycolysis Immunoblotting In Situ Nick-End Labeling Interleukin-4 Lymphoma Male Mice Mice, 129 Strain Mice, Inbred C57BL Mice, Knockout Mitochondria Oxidative Phosphorylation Poly(ADP-ribose) Polymerases STAT6 Transcription Factor Survival Analysis

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