First Author | Cho SH | Year | 2011 |
Journal | Proc Natl Acad Sci U S A | Volume | 108 |
Issue | 38 | Pages | 15972-7 |
PubMed ID | 21911376 | Mgi Jnum | J:176646 |
Mgi Id | MGI:5292397 | Doi | 10.1073/pnas.1017082108 |
Citation | Cho SH, et al. (2011) Glycolytic rate and lymphomagenesis depend on PARP14, an ADP ribosyltransferase of the B aggressive lymphoma (BAL) family. Proc Natl Acad Sci U S A 108(38):15972-7 |
abstractText | 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. |