title: Regulator of G-protein signaling 19 (RGS19) and its partner Gα-inhibiting activity polypeptide 3 (GNAI3) are required for zVAD-induced autophagy and cell death in L929 cells.
abstract: Autophagy has diverse biological functions and is involved in many biological processes. The L929 cell death induced by the pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-(OMe)-fluoromethyl ketone (zVAD) was shown to be an autophagy-mediated death for which RIP1 and RIP3 were both required. It was also reported that zVAD can induce a small amount of TNF production, which was shown to be required for zVAD-induced L929 cell death, arguing for the contribution of autophagy in the zVAD-induced L929 cell death. In an effort to study RIP3 mediated cell death, we identified regulator of G-protein signaling 19 (RGS19) as a RIP3 interacting protein. We showed that RGS19 and its partner Gα-inhibiting activity polypeptide 3 (GNAI3) are involved in zVAD-, but not TNF-, induced cell death. The role of RGS19 and GNAI3 in zVAD-induced cell death is that they are involved in zVAD-induced autophagy. By the use of small hairpin RNAs and chemical inhibitors, we further demonstrated that zVAD-induced autophagy requires not only RIP1, RIP3, PI3KC3 and Beclin-1, but also RGS19 and GNAI3, and this autophagy is required for zVAD-induced TNF production. Collectively, our data suggest that zVAD-induced L929 cell death is a synergistic result of autophagy, caspase inhibition and autocrine effect of TNF.
authors.affiliation: Department of Basic Medical Sciences, Cancer Research Center, Medical College, School of Life Sciences, Xiamen University, Xiamen, Fujian, China; State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Yuanyue
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Deli
authors.initials: D
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Felicia
authors.initials: F
authors.lastname: Han
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Duan-Wu
authors.initials: DW
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Jiahuai
authors.initials: J
authors.lastname: Han
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D020710:RGS Proteins / Q000378:metabolism*; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000494:pharmacology
chemical_list: D009842:Oligopeptides; D020710:RGS Proteins; D014409:Tumor Necrosis Factor-alpha; C517629:benzyloxycarbonyl-valyl-alanyl-aspartic acid; C097187:regulator of G-protein signalling 19; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C485615:Ripk3 protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; C417708:Gnai3 protein, mouse
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