Glycolytic rate and lymphomagenesis depend on PARP14, an ADP ribosyltransferase of the B aggressive lymphoma (BAL) family
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 glycolys...
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Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2011-09, Vol.108 (38), p.15972-15977 |
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Sprache: | eng |
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Zusammenfassung: | 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. |
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ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.1017082108 |