title: Glycolytic rate and lymphomagenesis depend on PARP14, an ADP ribosyltransferase of the B aggressive lymphoma (BAL) family.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Cho
authors.forename: Annie K
authors.initials: AK
authors.lastname: Ahn
authors.forename: Prerna
authors.initials: P
authors.lastname: Bhargava
authors.forename: Chih-Hao
authors.initials: CH
authors.lastname: Lee
authors.forename: Christine M
authors.initials: CM
authors.lastname: Eischen
authors.forename: Owen
authors.initials: O
authors.lastname: McGuinness
authors.forename: Mark
authors.initials: M
authors.lastname: Boothby
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005947:Glucose / Q000378:metabolism / Q000493:pharmacokinetics; D006019:Glycolysis; D015151:Immunoblotting; D020287:In Situ Nick-End Labeling; D015847:Interleukin-4 / Q000494:pharmacology; D008223:Lymphoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis
chemical_list: D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015847:Interleukin-4; C522628:Parp14 protein, mouse; D011065:Poly(ADP-ribose) Polymerases; D055372:AMP-Activated Protein Kinases; D005947:Glucose