JPOST Repositoryapplication/xmlhttps://storage.jpostdb.org/JPST000454/files/140306iwa_Hayashi1_65min_TOP20_4ul.xlsxhttps://storage.jpostdb.org/JPST000454/files/140306iwa_Hayashi1_65min_TOP20_4ul.msfhttps://storage.jpostdb.org/JPST000454/files/140306iwa_Hayashi1_65min_TOP20_4ul.rawprimary200OKProteomicsTetsu AkiyamaHomo Sapiens (human)https://repository.jpostdb.org/entry/JPST000454the University of TokyojPOSTGlioblastoma is one of the most aggressive forms of cancers and has a poor prognosis. Genomewide analyses have revealed that a set of core signaling pathways, the p53, RB, and RTK pathways, are commonly deregulated in glioblastomas. However, the molecular mechanisms underlying the tumorigenicity of glioblastoma are not fully understood. Here, we show that the lysine deacetylase SIRT2 is required for the proliferation and tumorigenicity of glioblastoma cells, including glioblastoma stem cells. Furthermore, we demonstrate that SIRT2 regulates p73 transcriptional activity by deacetylation of its C-terminal lysine residues. Our results suggest that SIRT2-mediated inactivation of p73 is critical for the proliferation and tumorigenicity of glioblastoma cells and that SIRT2 may be a promising molecular target for the therapy of glioblastoma.SIRT2-mediated inactivation of p73 is required for glioblastoma tumorigenicity.Funato Kosuke K, Hayashi Tomoatsu T, Echizen Kanae K, Negishi Lumi L, Shimizu Naomi N, Koyama-Nasu Ryo R, Nasu-Nishimura Yukiko Y, Morishita Yasuyuki Y, Tabar Viviane V, Todo Tomoki T, Ino Yasushi Y, Mukasa Akitake A, Saito Nobuhito N, Akiyama Tetsu Tp73RhoGAP, TAp73, 293 T cell, 293T Cell, 293 Cells, RC-GAP72, HEK293T cell, p73, acetylation, Human Embryonic Kidney Cell Line 293, HEK293, Acetylations, Human Kidney Cell Line 293, HEK293 Cell, deltaNp73, RCGAP72, HEK 293 Cell, Cell, 293T cell, Tp73, 293T, HEK 293 Cell Line, HEK293., HEK 293 Cells, P73, Cells, HEK, 293T Cells, HEK 293, FILGAP, Trp73, 293 Cell, 293-T cellForms, Ras1/RAs85D, IPP2A2, dp53, RAS, Ras, Activity, Lysine Hydrochloride, E(sev)3C, Ras-1, Astrocytomas, betaTub3, Tp53, 5730420M11Rik, ras, Lysine Acetate, DMP53, bbl, Mother Cells, 2, Dmp53, deacetylation, D-Ras1, L Lysine, treatment, SET, 1323/07, RC-GAP72, Prognoses, RTK, BCC7, TAF-I, K, beta-Tub6D, dmp53, epsilon-diaminocaproic acid, T, DmP53, 1422/04, ras85B, ras85D, Giant Cell Glioblastoma, Astrocytoma, Tp73, DmelCG4299, IGAAD, set, B3t, DmelCG3401, LYS, DmelCG10574, Dp53, grade IV adult Astrocytic tumor, Lysin, disease management, Therapies, CG17117, Grade IV., p50/tubulin, single organism signaling, p73RhoGAP, phapii, Therapy, CG10873, l(3)s1747, Ras1, RAS1, D.mel2, StF-IT-1, Giant Cell, RCGAP72, results, 3t, SIR2L, Colony-Forming Unit, Stem Cell, primary glioblastoma multiforme, SIRT2, dRas85D, lysine, p21[Ras1], bfy, dRas1, dRAS1, ras1, Dras85D, Tub60D, HTH, Hth, Mother Cell, beta-tub, Glioblastoma, Factors, HLA-DR-associated protein II, DI-2, spongioblastoma multiforme, Prognostic, I-2Dm, D-ras1, Stem, SIR2, DmelCG33336, GBM, CG3401, C-ras1, beta3Tub, beta3TUB, Dm Ras1, Colony Forming Units, CG4299, alpha, deltaNp73, Treatments, l(3)06677, I-2PP1, DTB3, RasI, sir2, hth1, TAF-IBETA, hth2, Grade IV Astrocytomas, Cells, P53, p44, bhy, TAF-Ibeta, Sir2l, i2pp2a, CG31325, betaTub, Prognostic Factor, beta[[3]]-Tub, TAp73, DmelCG17117, p50, RasV12, dRas, p53, Colony-Forming Units, SIR2L2, Progenitor Cell, DRAS1, Prognostic Factors, 143391_i_at, beta3 TU, DmelCG9375, Grade IV, LFS1, PHAPII, l(3)05745, Dras1, D-Ras, P73, glioblastoma, Lysine, Silent Mating Type Information Regulation 2 Homolog 2, anon-EST:Liang-2.13, Giant Cell Glioblastomas, Sirt2, Progenitor, Trp73, Dras, ras 1, dras1, grade IV adult astrocytic tumor, clone 2.13, D.m.BETA-60D, p73, ipp2a2, 2pp2a, sirtuin, Mother, Ras[V12], EK3-4, CG10574, DRas, DRas85D/Ras, Ras 85D, Glioblastoma Multiforme, Trp53, 2PP2A, taf-ibeta, CG5085, dSIRT2, betaTub60C, dSET, dSet, beta3-tubulin, Grade IV Astrocytoma, beta[[3]]-tubulin, TRP53, beta-Tub60D, grade IV adult astrocytic tumour, Colony Forming Unit, Dmbeta3, Dm-HTH, CG9375, BETA 60D, Progenitor Cells, prac, igaad, beta3t, beta3-Tub, Factor, D-ras-1, Cell, group, Xp53, E(faf), adult glioblastoma multiforme, fs(3)05703, I-2PP2A, Acetate, p53/tubulin, Dm I-2, I2PP2A, S35097, core, FILGAP, beta[[3]] tubulin, L-Lysine, DmelCG5085, glioblastoma multiforme, CG33336, RAS85D, Dmras85D, ensemble, D-p53, Glioblastomas, beta60C, Dm-P53, l(3)86Ca, beta3, Su(tor)3-2, dtl, Tub, dSET/TAF-Ibeta, Meis1, 2610030F17Rik, 5730427M03Rik, signalling process, Therapeutic, betatub60D, Treatment, AA407739, 6-diaminohexanoic acid, Enisyl, General activityp73RhoGAP, TAp73, glioblastoma multiforme, grade IV adult astrocytic tumour, RC-GAP72, Glioblastoma, grade IV adult astrocytic tumor, D.mel2, spongioblastoma multiforme, p73, SIR2L2, SIR2, Glioblastomas, GBM, sirtuin, deltaNp73, Giant Cell, Grade IV, Giant Cell Glioblastoma, RCGAP72, Astrocytomas, Astrocytoma, Tp73, SIR2L, sir2, adult glioblastoma multiforme, Glioblastoma Multiforme, 5730427M03Rik, Grade IV Astrocytomas, CG5085, grade IV adult Astrocytic tumor, primary glioblastoma multiforme, P73, SIRT2, dSIRT2, glioblastoma, Sir2l, Silent Mating Type Information Regulation 2 Homolog 2, Grade IV Astrocytoma, FILGAP, Grade IV., Sirt2, Giant Cell Glioblastomas, Trp73, DmelCG5085TAp73, F10B6_15, Reverse, Immunoelectroblotting, 293tsA1609neo, Immunoblotting, chlorure d'hydrogene, SIR2L2, classic hairy cell leukaemia, Dot Immunoblotting, Gene, SDH, Hydrogenchlorid, protein, protein-containing complex, F10B6.15, 293T, Buffer, SDS, halite, Electroimmunoblotting, hydrogen chloride, Dot, congenital, P73, Gene Products, Silent Mating Type Information Regulation 2 Homolog 2, deacetylation, protein aggregate, Sirt2, Trp73, cloruro de hidrogeno, RCB2202, HEK293T, RC-GAP72, 293-T, Hydrogen chloride, Immunoblottings, p73, chlorure de sodium, Acetylations, sirtuin, 4733401P19Rik, lipomatosis of pancreas, Tp73, Hek 293T, cloruro sodico, salt, reaction, Wasserstoffchlorid, HEK-293T, SOLO DANCERS, CG5085, congenital lipomatosis of pancreas, sample, dSIRT2, Kochsalz, Shwachman-Bodian syndrome, Immunoelectroblottings, p73RhoGAP, Human Embryonic Kidney 293T, rock salt, D.mel2, protein complex, Proteins, acetylation, AI836084, HEK 293 T, chloridohydrogen, classic hairy cell leukemia, RCGAP72, buffer, Cell, SIR2L, [HCl], common salt, native protein, Dot Immunoblottings, Natriumchlorid, SIRT2, Protein, Chlorwasserstoff, Hydrochloride, table salt, FILGAP, NaCl, Reverse., DmelCG5085, Reverse Immunoblottings, Electroimmunoblottings, HCl, SIR2, Shwachman-Diamond type metaphyseal dysplasia, SWDS, Shwachman-Bodian-Diamond syndrome, deltaNp73, Shwachman syndrome, CGI-97, natrii chloridum, 293 T, sample population, Protein Gene Products, Gene Proteins, sir2, 5730427M03Rik, Reverse Immunoblotting, Pancreatic insufficiency and bone marrow dysfunction, Sir2l, chlorane, hydrochloric acid, HEK-293-TfalseAcetylation of p73 in 293T cell293T cells ectopically expressing FLAG-tagged p73 were treated with AGK2 and p73 was immunoprecipitated. The precipitants were resuspended in deacetylation buffer (50 mM Tris-HCl pH 8.0, 140 mM NaCl, 2 mM MgCl 2 ) and incubated with recombinant SIRT2 protein (10 U). The reaction was terminated by boiling with SDS sample buffer and acetylation levels were determined by immunoblotting.Mon Sep 10 00:00:00 BST 2018PXD010411960630213795