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Zeidan Q, Tian JL, Ma J, Eslami F, Hart GW. O-GlcNAcylation of ribosome-associated proteins is concomitant with translational reprogramming during proteotoxic stress. The Journal of biological chemistry 2024 300(11) 39395807
Abstract:
Protein O-GlcNAc modification, similar to phosphorylation, supports cell survival by regulating key processes like transcription, cell division, trafficking, signaling, and stress tolerance. However, its role in protein homeostasis, particularly in protein synthesis, folding, and degradation, remains poorly understood. Our previous research shows that O-GlcNAc cycling enzymes associate with the translation machinery during protein synthesis and modify ribosomal proteins. Protein translation is closely linked to 26S proteasome activity, which recycles amino acids and clears misfolded proteins during stress, preventing aggregation and cell death. In this study, we demonstrate that pharmacological perturbation of the proteasome-like that used in cancer treatment- leads to the increased abundance of OGT and OGA in a ribosome-rich fraction, concurrent with O-GlcNAc modification of core translational and ribosome-associated proteins. This interaction is synchronous with eIF2α-dependent translational reprogramming. We also found that protein ubiquitination depends partly on O-GlcNAc metabolism in MEFs, as Ogt-depleted cells show decreased ubiquitination under stress. Using an O-GlcNAc-peptide enrichment strategy followed by LC-MS/MS, we identified 84 unique O-GlcNAc sites across 55 proteins, including ribosomal proteins, nucleolar factors, and the 70-kDa heat shock protein family. Hsp70 and OGT colocalize with the translational machinery in an RNA-independent manner, aiding in partial protein translation recovery during sustained stress. O-GlcNAc cycling on ribosome-associated proteins collaborates with Hsp70 to restore protein synthesis during proteotoxicity, suggesting a role in tumor resistance to proteasome inhibitors.
O-GlcNAc proteins:
RL1D1, TBB4A, PAI1, RLA0, RS17, BIP, HSP7C, RS2, RL35A, RL17, NUCL, RS3, RL29, RL13, RL9, HS71L, PHB1, RS19, RL28, RS5, RL14, HMGA2, ACTB, RS20, RS3A, RL26, RL15, RL37A, RS8, RS14, RS23, RS18, RS13, RS4X, RL23A, RS15, RS25, RS28, RL8, RS21, RL24, RLA2, RL18A, SSBP, RL18, ILF2, RS27L, RL51, DDX21, ATD3A, RRBP1, EIF3L, RM11, FARP1
Species: Rattus norvegicus, Homo sapiens, Mus musculus, Arabidopsis thaliana
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Hung YW, Ouyang C, Ping X, Qi Y, Wang YC, Kung HJ, Ann DK. Extracellular arginine availability modulates eIF2α O-GlcNAcylation and heme oxygenase 1 translation for cellular homeostasis. Journal of biomedical science 2023 30(1) 37217939
Abstract:
Nutrient limitations often lead to metabolic stress during cancer initiation and progression. To combat this stress, the enzyme heme oxygenase 1 (HMOX1, commonly known as HO-1) is thought to play a key role as an antioxidant. However, there is a discrepancy between the level of HO-1 mRNA and its protein, particularly in cells under stress. O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins (O-GlcNAcylation) is a recently discovered cellular signaling mechanism that rivals phosphorylation in many proteins, including eukaryote translation initiation factors (eIFs). The mechanism by which eIF2α O-GlcNAcylation regulates translation of HO-1 during extracellular arginine shortage (ArgS) remains unclear.
O-GlcNAc proteins:
TVBY1, TX13D, CC195, SPEM3, TVB42, FR1L5, HFM1, CCD66, SBNO1, Z804B, LRRD1, XIRP2, POTEF, PSD1, BDP1, NKX26, SWAHB, F181B, SMCO2, MGT4D, CAN8, EPOP, SMHD1, AKD1B, T200C, AQP73, AXA2L, NTM2B, ZAR1L, AN36A, NEU1B, GG6L6, B2R853, KDM4E, HNRC2, ERVV1, HNRC3, TEX22, TM232, MEIOS, CK098, SO1B7, TEX46, KIF2A, BACH, MYO1C, AP3B1, IKBE, HIP1, TULP1, WASL, PDE2A, SAP18, DNM1L, IFRD1, ZN593, FAAH1, PESC, SDCB1, MPP10, NOP56, DDX3X, CCN1, PLPP3, NCKP5, AGRB1, AP3D1, IDLC, CHD1, CHD2, PDCD5, ANM5, H17B6, FPGT, TCRG1, KIF3C, GEMI2, ML12B, CLGN, MYPT1, S27A2, XPO1, AT2A1, PLXB2, SR140, PER2, GRRE1, MCF2L, NACAD, ATS3, ANR28, VILL, LAMA5, MATN3, ATX7, INP4B, TRI18, GPR37, RPA34, MAGB3, PER1, KDM6A, DHX15, TTI1, PRP4, SERA, ADA12, IRAK2, ZW10, SNUT1, SPIT2, SRGP3, VIP2, PRPF3, GRID2, TGON2, LAT, SYT7, PLRG1, BUB3, PLPP2, PI15, ACTN4, SCO2, IDH3B, CALU, AGRB3, MED14, FGF17, PRKN, JIP4, KIF5C, ZC3H1, KATIP, OPA1, KIF1B, NMD3B, PEPL, PLXC1, ADCY9, HNRPQ, TPST1, RNBP6, CCNT1, FAIM3, ANM3, HCN1, RT14, HNRC1, H2B1K, PQBP1, PRAF2, DKC1, IF2P, TRI13, DNJA2, BRD4, NBN, IGSF3, DEN4B, ADA23, MFA3L, CLAP2, OBSL1, BRE1B, RFIP3, KDM4A, DJC13, ANR17, ZPR1, NIPS2, HMMR, ZN217, SC22B, PR40A, DPOLQ, ZN254, PSIP1, ERLN1, ECI2, KHDR3, TADA3, SF3B1, MED6, FOXH1, SPB7, U520, UTP20, TCEA3, SPI2, KLF7, MMP23, RASF9, CCNK, PRAF3, DYSF, SPF27, ATP5H, TRIO, RL1D1, NEBL, OCTN2, PDE9A, SRP72, B3GA3, UBP1, SLIT2, TOM70, MICA2, NFASC, FARP2, ERLN2, PRP6, GLSK, RNF37, WDR47, AP2A2, CE152, HEXI1, UBE4B, CSPG5, LETM1, LC7L3, KIF4A, GOSR1, KAT7, MRP6, TNKS1, KCNK5, VAPB, IPO7, M3K6, UTS2, CD2B2, FMNL1, SGPL1, G6PE, SC24A, ACSL3, DUS4L, ZBT11, CPSF4, K2C75, HERC2, SNP29, AP2A1, WIZ, STAU1, BAG2, ONEC2, TOP3B, APCL, PX11B, PAK4, LDHA, NB5R3, F13A, MOS, PGK1, TRYP, OVAL, IGHG1, IGHG2, IGHG3, IGHG4, HLAH, HBE, LMNA, ALBU, VTDB, TRFE, FRIH, MIS, VTNC, TDT, ALDOA, ANXA1, APOB, OAT, K2C1, SEMG1, TBB4A, G3P, NTRK1, P53, HSPB1, RPN1, RPN2, B3A2, AT1A1, CP17A, ITB2, HMGN1, CFAI, PCCA, IF2A, HMGN2, RLA1, RLA2, RLA0, AP2A, INSR, AGAL, RB, CDK1, ATPB, ENOA, NPM, TPM3, H2B1J, LDHB, H10, CATD, ANXA2, CO8A, TBB5, PROF1, HS90A, HNRPC, TPM2, GLI1, ACM2, CEL2A, HS90B, SRPRA, ODPA, CO4A2, MET, RU17, VIME, RS17, K2C7, ANXA5, K1C16, RSSA, GSTP1, RU1C, VILI, HMGB1, TPM1, WNT2, ROA1, C1S, PARP1, H2BFM, ATX1L, MYZAP, ZCC18, POTEI, POTEJ, SP9, UBB, UBC, MPC1L, ST1A4, HS71B, C1C1L, IGG1, D130B, M14OS, TBA3D, PR20G, TZAP, ACRO, H14, ODP2, THIO, PPGB, CH60, THA, BIP, HSP7C, ODPB, PYGB, PYGM, BCR, SPTB1, TOP1, PYC, DMD, C1TC, PABP1, K2C3, CO6A2, SKI, FETUA, ACTN1, MYH7, XRCC6, XRCC5, EF2, K1C10, K1C13, K2C5, TNNT1, COBA2, SUIS, KPYM, ENPL, CCNB1, HNRPL, MYOD1, EZRI, AREG, NQO1, RS2, CD44, H15, H13, H12, YBOX3, ZNF18, ZN182, ZNF43, HSP76, HMGA1, ZNF8, KPCA, CXA1, UBF1, DESM, NEUM, CR1, IBP3, TCPA, ITB5, RL7, SON, RL17, SDC1, K2C4, NUCL, E2AK2, CSK22, NCF2, FST, IF2B, ANXA7, CD33, BTF3, TNR1B, RAB3B, CAN3, ICAL, CO5A1, PHOS, CD11B, CSRP1, FLNA, PERL, TENX, PUR6, UBA1, H1T, ROA2, SAV, FBLN1, TCEA1, ITA6, SFPQ, PPIB, RS3, PTPRE, H2B1O, COF1, IF4B, CPT2, CCND1, RAE1, KPCL, THIL, RPB1, LAMA1, DNJB1, ATPA, DDX6, CTNA2, DNMT1, U2AF2, RL13, S10A4, HMGB2, PTBP1, HGFL, STOM, PON1, 1433T, RL10, CALR, MAP4, CALX, PSA5, ABCD3, LYOX, HXD10, PTPRM, PTN4, T2EB, EPHA2, EPHA8, TKT, LMOD1, EF1D, RL12, PDIA3, 2AAA, MPIP3, BKRB2, NKTR, KPYR, SDHA, HXA10, HXA9, GBRA5, DNJA1, AKT1, HNRH1, 1433B, S10AB, P5CR1, IFNA8, DSG3, RL9, KINH, CP2CI, H2B1B, EVI2B, HS71L, HSP74, PHB1, MERL, RADI, RL22, T2FA, SCN1A, K1C9, FBN1, FBN2, IRS1, MYH9, MYH10, COPB2, SOAT1, FUS, DEK, CYLC1, MYH11, AHR, K22E, ACHA7, RL4, LONM, ACV1B, SRP14, ZEB1, TAGL2, BRCA1, VATA, GRP75, RS19, RL3, OST48, FEN1, TXLNA, TCPZ, ARL1, UBP8, RFC3, ECHA, IF2G, PERI, BUD31, NAA10, KDM5C, GARS, SYIC, NBL1, LAP2A, LAP2B, EPS15, RS27, LPPRC, RL35, PF2R, MUC18, MATR3, GPDM, RANG, NAMPT, EFTS, KI67, RAGP1, ATRX, IF2M, BAG6, RL27A, RL5, RL21, RS9, RS5, RS10, MAP1B, IQGA1, IF1AX, OMP, RL29, ATPO, TCPE, K2C6C, KC1A, MASP1, HSP77, TCPG, EFTU, SRP09, SYAC, SYCC, SYSC, YLPM1, TMEDA, RBM25, TSC2, GUAA, ENTP1, MEOX1, ST1A1, ST1A2, GATM, SERPH, KNTC1, CDK9, R144A, RL14, TCPQ, TCPD, FXR1, RAB7A, ZNF83, SSRD, AL3A2, DHB4, PSMD7, CCL11, ZNF41, ROA3, MYOM1, HNRPM, IMA1, IMA5, MP2K6, HNRPF, MSH6, HMGA2, CRIP2, COPB, COPA, CRBB1, SMTN, MOT1, IST1, SC24C, TCP4, SYRC, ATX3, TERF1, SYYC, HSP72, ATNG, EPHA4, GYS2, DRG2, XPO2, MFAP1, PAR2, BRPF1, NP1L1, ANM2, PSA, EIF3B, SYMC, HDAC4, IF6, RP1, NRG3, H2BFS, UBS3A, WDR4, SNX16, SELB, SESN2, H2B1D, NAL11, DJB13, TPIS, MYPR, MYL6, ACTB, IF4A1, RS20, S10AA, CDC42, DEST, SRP54, RAB2A, RAB14, ZC3H6, ACTZ, ARF3, ABCE1, RS3A, RL26, RL15, RL27, RL37A, DCAF7, HNRPK, RRAS2, RS7, RS8, RS15A, RS16, 1433E, RS14, RS18, RS29, RS13, RS11, SMD1, SMD2, ARF6, RL7A, RS4X, ACTA, RL23A, RS6, VISL1, H4, H2B1C, RAB1A, RAN, RL23, RS15, RS24, RS25, RS26, RS30, RL39, RL31, RL10A, RL32, RL11, RL8, PPIA, RS27A, RL40, TRA2B, AP2B1, 1433Z, 2ABA, RL38, RACK1, ACTG, ACTH, YBOX1, CSK2B, TPM4, ACTC, EF1A1, ACTS, TBA1B, TBA4A, TBB4B, CSK21, HBG1, HBG2, NOP14, RPP30, PHC1, S35A1, PRKDC, M3K9, SSBP2, RT22, RT11, RT09, ATL3, RL24, RL19, SRSF3, MUC5A, TFAM, CLH1, NFKB2, HNRPU, MYPC1, MDM2, U2AF1, AMPD2, DIAC, CAP1, K22O, CAC1D, EXOSX, PFKAP, EWS, CO4A3, AK17A, CENPE, MMSA, BDH, DSG1, H11, GHRHR, M3K10, PLOD1, RL6, PO3F1, CAV1, KMT2A, TAP2, ZN117, IF4G1, SRS11, EF1A2, CALD1, AT5G2, PTN11, GABP1, ZN33A, FMR1, PRDX1, RL18, C1QBP, CKAP4, PDE4B, KHDR1, SLC31, SOS2, SRSF1, ACTN3, TLE5, SRSF4, DHX9, GOGA2, DSC1, SSRP1, CAMP2, NSUN2, AHNK, DIK1C, LR74A, LMOD3, CF210, GALT2, AP1B1, HMGX3, NU160, TBL3, TF3C1, ASPH, TROP, BPTF, CNTN1, SFSWA, CHD3, SF3A3, NMDE1, TP53B, ILF3, TIAM1, AKAP6, FLII, TRDN, ACACA, ZBT17, REST, TADBP, ROA0, CBX3, STK3, CBLB, DNJC3, M3K1, SRSF6, I15RA, G3BP1, ATM, AP3B2, PPIG, TCOF, SF3B2, GOGA4, ROCK1, TOP3A, SQSTM, MED21, MTX1, TBB3, PRP4K, ATR, KCC2D, TDG, SNW1, DGKZ, CUL1, S12A1, MOGS, NACA, THOC5, NOG2, PTK6, TBB2A, CAC1C, CKAP5, CO4A6, LRP8, PDE1C, BOP1, SEPT6, MORC3, EFR3A, UBP2L, SIM2, DYHC1, ELOA1, TRI25, MYPC2, FRG1, CAPR1, RBM39, SCN5A, PDIA5, HS902, ZN266, ZN235, SMC1A, RRP1B, NCOA6, GANAB, 2A5D, MVP, LTBP1, GOGB1, GRM7, CHD4, LASP1, RB39A, IMB1, PSME4, CUL7, NAA25, RTP5, MO4L2, SEPT2, SUZ12, U5S1, BRD3, EEA1, PDIA6, PCOC1, PDK2, PLEC, PCM1, NONO, RASA2, RNPS1, PCBP1, PCBP2, SF3B3, RYR3, CNN3, SF3B4, RBMS2, SF3A1, SIX1, MED22, TRAM1, SF01, TRIPB, OASL, MED1, TRIP6, TWST1, PI5PA, CEBPE, AAAT, TOM34, NCOA1, GRK1, SCN9A, ZYX, SEPT7, UAP1, GBRA6, CSRP2, CDC37, IL17, DPYL2, M3K11, SRSF7, CPSF6, AT2B3, H2A2C, H2B2E, HCDH, FA98C, TIGD6, NKPD1, KNOP1, ESRG, PDS5A, MOONR, BLTP1, KIF7, TSR1, C19L2, CO3, PRTG, GAB4, ZN750, P3H1, RA1L2, MA7D1, CHD9, TKFC, PTHB1, RABL6, TBB8, CRFM7, GLYR1, C2CD3, LARP7, TB10B, A20A4, GRAP1, MIDN, PKDCC, CN177, CEP55, KLH22, PLA1A, SGO2, ACTBL, BRDT, H90B4, H90B3, H90B2, HS905, ODFP2, ESCO1, SH319, AN36C, PPM1J, FGD3, RRP12, CF157, ZN484, GNAS1, GASP1, EOGT, BRM1L, H2B2F, PPM1L, TM201, CA167, TT39A, HP1B3, CE170, FREM2, CE85L, SZT2, AXDN1, EYS, ZC3HD, GPTC4, RBM20, UBR4, GNTK, ER6L2, HENMT, TTC22, FRY, B2L15, KAD9, M3K21, DDI2, MROH9, EFCB6, A20A1, CROCC, CL060, OBSCN, FA78B, EF1A3, PR38B, BRE1A, SMBT2, SPO16, TASO2, MALR1, ECM29, SHE, NAA35, TM268, RES18, K2C79, KFA, WSCD1, F91A1, CP135, AR6P4, MROH7, UTP25, RHG17, Z518A, SCAR3, KDM4D, IQEC1, XAF1, OVOS1, CAPR2, IQCE, ZN770, F166A, NIPBL, LIN54, TET2, TEN4, OGFD2, TM214, CAVN1, CDC73, ARMX5, MED27, ANM9, PRP8, PLBL1, NFRKB, ALKB5, TRI40, TBA3E, PONL1, TTC33, MYO7B, RICTR, BRWD3, POTEE, POTEA, CC171, S4A10, FIP1, PRS55, LRSM1, SBSN, CLM9, LRIG3, RSPO2, TMC5, RFIP1, CD109, HSDL2, B3GN6, CCNI2, M3K15, LN28B, NFXL1, DYH12, RN207, ITPI1, CRACD, YC006, PLPL7, FGD6, PHLP2, ANKS3, YS043, NEK10, KRA55, KRA52, VP13C, UBP34, RAPH1, UBP51, UBP45, UBP50, IKIP, MD13L, TBA1A, B4GN4, ATS13, HECW1, BT2A1, SND1, DDX46, TM10C, RSRC2, DET1, H2A3, FAKD5, NLRC3, SSX6, MOT9, OVCH1, PLPR4, PCLI1, NRK, MON2, K1C28, K1C27, K1C25, CSMD3, NUFP2, SZRD1, NPHP3, TT21B, GDF7, KI21A, CFA91, ZN438, HDGR2, SDK1, SPRE1, SRGP1, RBBP6, NECA2, SH3R1, SEN54, K2C1B, CNTRL, CTU1, RM55, VP13B, AGRE4, GLRX5, ZN605, DAAM2, K1328, PATL1, DDX53, TRPT1, LYRIC, AKA28, KTN1, GTD2A, ABCAD, EST1A, PHLB1, LUZP1, THOC4, IFTAP, LRRT4, ZCH18, ARHGP, MON1A, THOC6, AMGO1, AMGO3, AROS, CHSS1, DDX42, NIBA3, CEP57, DAAF5, LYPD6, STX12, DZIP1, HORN, KLOTB, WFDC8, GLT13, ZDH13, CRLF3, CRERF, ARMC8, K0825, ANKY2, AHNK2, DYH10, P3H2, SPNS2, VSTM4, WDFY1, PHF6, SULF2, CHERP, ANKH1, PHC2, OD3L1, F217A, DDIAS, RB12B, SP8, DDX60, RAVR1, SPB1, DRC7, EFC13, CKP2L, SRRM1, CCD13, ELOA2, CC105, ZN100, SMYD4, MICU2, CFA46, RN168, CHSS2, RTKN2, DOCK3, AGRF3, XRN1, ASPM, DSEL, RBIS, SPICE, TAGAP, NDUF2, VPS52, LRC47, K2C78, MYO1H, KLH34, H2B3B, ANR35, GAPT, UB2J2, AN36B, LAT4, EH1L1, PALS1, FNBP4, GUF1, RIBC1, NIN, ZN276, ZN561, SRBD1, NKAP, MACOI, PAR16, AADAT, IQCF1, EFNMT, KLDC1, PLD5, ANR31, CDYL2, AMER3, NEPR1, YJ012, MUT7, BANP, SR1IP, TOPZ1, CO053, PR38A, UBP38, UN13C, FANCB, GOLM1, GT251, DHB11, TM145, SERB1, DYHC2, CC020, GIMA8, TNR6A, ZN740, DIK2A, ZN738, ABCF1, DUS18, ZN548, EXPH5, KMT2C, ABHDB, MYRIP, KNL1, RDM1, O52E5, DDX55, MAFA, ZFP28, THOC2, KCNG3, TTC8, PI42C, TBC15, MIEAP, CIP2A, ZN507, CERK1, BICD2, CHD6, HELQ, CHD5, KCNG4, BRX1, CLM1, OTU7A, ATS16, DYH5, DQX1, TP4AP, WHAMM, UBS3B, AT8B4, SHRM3, WIPF2, F222B, ZC3HF, PPIL4, CCD12, HDAC7, PDC6I, CATIN, CO040, SFT2A, SNR27, HNRLL, UBCP1, CQ050, CTL1, CKAP2, SPIR2, ATX2L, ABCAA, SREK1, CRGN, SYNE2, MUC16, P66B, DNJC9, TITIN, DDX1, H1X, TM131, IP6K1, AP3S1, HS105, SEPT8, PRP16, AN32B, TFG, AP2C, STAM1, DPF3, REQU, RBP56, EVPL, DDX17, KIFA3, SEM4D, XPF, SMRD2, RAB1C, FUBP2, KCNB2, USP9X, UBP7, CUL5, VPP1, MED12, TATD2, H2B1H, FBXW7, YIPF5, UBE2F, RL36L, GTPB3, H2B1A, CCD47, FERM2, PLPL2, LRC59, PBIP1, TTC28, BORC7, SPSB1, ANKR9, CC127, DOC10, P5CR2, ROP1L, FAF2, ZN689, AP2M1, NTNG2, KCD12, PGBD4, MTBP, RMXL1, HOOK2, RBM33, DTBP1, TMA16, ALG14, CPNE2, KIF12, SIPA1, THOC1, RM48, DDX27, P121A, TONSL, PDLI5, PGAM5, COX14, AJUBA, A26L1, PAWR, VPS50, JPH4, NEUL4, HSH2D, ZN514, AGRG7, RPGR1, ZFR, NAR5, ALPK3, IFT74, PPR36, LRGUK, DNHD1, KLH15, ZN512, RIPR3, RN145, CFA44, ZDH15, PWP2A, DOCK7, ZN830, BROMI, SCLT1, CNT3B, ANR27, GP101, IPO9, LRC3B, PGRP2, INP4A, ADCYA, GBP4, ZN317, NED4L, SLIK1, NEK1, PP1RA, XPO6, H2A1A, MAGI1, SNX18, S26A8, MCCA, CTGE2, HMCN1, S22AC, RANB9, CCNL2, SMC6, ZN347, STRBP, SIN3A, RBM15, PNKP, SETB2, NIBA2, SCN2A, NELL2, PSB7, SEC62, CDC5L, STAC, AGAP2, GA2L1, DNJC2, PHB2, KIF2C, HCD2, CPNE1, EBP2, H2B1N, H2B1M, H2B1L, MYOC, SEM3C, GDF15, AKAP9, MICU1, TRIR, SLX1, MEP50, TBA1C, SELS, MBB1A, SYT3, NRIP2, FYCO1, GPTC1, RIOK1, LLPH, WDR83, S35A5, PIMRE, SOX7, WAC, MTA3, MCMBP, MED10, LRRC1, TBB6, HNRL1, DDX23, TBB2B, TMED9, RIOK2, ELOV1, RFIP5, ASPN, AP1M1, NUSAP, TDRD1, EMIL2, AN30B, SCAPE, RTF2, DUS16, MK67I, HOIL1, RT26, KRA41, SETD2, TBD2A, ACTBM, CNTP3, PC11X, PC11Y, PUS3, UACA, REN3B, CRNL1, EDEM3, UBXN6, API5, ZFHX2, CFA74, CE295, ASXL3, ZN407, LRC27, WDR12, IMUP, SENP6, CHST5, WN10A, EGLN1, PEG3, CHST6, NACA2, PAIP1, LSG1, KLC2, ZN541, INT2, DDX47, F234A, NUCKS, S6A17, ABCG5, EHD4, P2Y12, VPS11, TARA, SLK, TNKS2, RBP17, RM46, PININ, SNX25, MOD5, MTRFR, HRH4, NDST4, PTN23, SEM6B, MFSD1, PIGU, PLK3, FA83D, TRABD, EHD1, MROH8, PDZD7, TFB2M, DHX35, ZN576, BICC1, Z385D, CCD86, PRR36, RANB3, AT133, NRDE2, METL8, ZN430, CAAP1, NOL11, ZFAN3, F204A, VRTN, MARH7, SFXN1, SPE39, VP37B, UBP42, KANL2, LN28A, EAF6, ZN556, LIN7B, RENT2, XPO5, CP343, MKNK2, UBP29, PLRKT, SPC25, GPR35, SPON1, LST2, TANC2, EPG5, K1586, ZBT26, FBSL, ZN334, SPCS, MYO10, APMAP, ZCC17, VTA1, SYSM, SIX2, DCP1A, MED4, GP108, LUC7L, SCUB2, RM40, CASS4, RTN4, IFT46, RPR1B, ANLN, BIRC6, DDX21, SAR1A, ASH1L, ARHG4, ARHG3, MXRA5, SPTN5, SNRK, STRN4, TRYG1, SOSSC, F1142, LTBP3, KRT84, DIAP3, PDS5B, SMC4, MA2C1, RN146, MDN1, LYRM2, SPS2L, ABCF3, MRGBP, SEP11, MED17, FANCI, DDX18, KLH11, RPC5, SDA1, CS073, ARGL1, PK1IP, HPIP, CB042, SDHF2, NHP2, LYAR, MED29, CWC25, THUM1, SCN3A, TBA8, DYH9, HXC10, FKB11, CELR1, CDK12, FMN2, RTEL1, IL36B, SACS, E2AK3, PA2GE, MYOF, BICRA, NOP53, HACD3, KCMF1, RAI14, VAPA, SLAF8, SIRPG, HCN3, DYH2, RCC2, TEN3, RRBP1, CPSF2, SYLC, ANKY1, HOP2, IKBL1, COPG2, MYOTI, P2RX2, SPAST, TRMB, FA8A1, DBF4A, MO4L1, MALT1, DAXX, MARCO, ZBT47, CGBP1, GCP4, KDM5B, SYWM, HMGX4, NOL12, ARMX3, SWP70, SUN2, AFF4, MKRN1, NPCL1, CHRD1, SEPT9, PCS1N, NB5R1, S30BP, PUF60, SCNBA, DNAI1, BAZ2B, PHF11, VAX2, RABX5, TRM6, ZN391, APC7, STML2, VPS28, CCNL1, FBX9, MRT4, PITC1, GPTC8, PARP4, MYO15, TF3C4, ADA28, NUP50, ZN236, ZN346, HCN2, ZN214, NRX1A, ZN608, MRTFB, ATD2B, NEB1, SHRM4, TMCC3, MYO5B, TPX2, NP1L2, MAFF, NOTC3, PRP19, G3BP2, RHG26, CHIP, MAGD2, SSRG, ING4, DIM1, TTF2, L10K, LIMC1, AGAP1, TNR6B, ZC3H4, THS7A, RIMS2, SRRM2, CTND2, BAIP2, SCN8A, PPR3C, LAMP3, RTRAF, RUVB2, LZTS1, TN13B, SYFA, SIGL7, DRG1, NCKP1, TLR6, ATF5, DIP2C, DLGP4, FYV1, KDM2A, TPPC8, KLH20, S27A6, YBOX2, TR150, WBP11, NOP58, NOSIP, LC7L2, SF3B6, ORN, NOP16, TIM16, RT23, RTCB, HCN4, ZN330, RL36, CCDC9, HBS1L, DMXL1, ZAN, KDM3A, MFHA1, PLXD1, HECD4, WDR7, IRS2, HYOU1, OARD1, SP16H, PCDGH, HEY1, SRPRB, O51B2, CORIN, DMRT2, MRCKB, NOX1, RBM8A, ZN706, SNX9, SCNAA, HCFC2, PUS1, MYH4, SPIN1, COPG1, CFA20, EMIL1, PTC2, DC1L1, STYL1, OAS3, TLL2, ZNT1, MYO16, GAK19
Species: Sus scrofa, Homo sapiens, Bos taurus, Gallus gallus, Streptomyces avidinii
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Berthier A, Vinod M, Porez G, Steenackers A, Alexandre J, Yamakawa N, Gheeraert C, Ploton M, Maréchal X, Dubois-Chevalier J, Hovasse A, Schaeffer-Reiss C, Cianférani S, Rolando C, Bray F, Duez H, Eeckhoute J, Lefebvre T, Staels B, Lefebvre P. Combinatorial regulation of hepatic cytoplasmic signaling and nuclear transcriptional events by the OGT/REV-ERBα complex. Proceedings of the National Academy of Sciences of the United States of America 2018 115(47) 30397120
Abstract:
The nuclear receptor REV-ERBα integrates the circadian clock with hepatic glucose and lipid metabolism by nucleating transcriptional comodulators at genomic regulatory regions. An interactomic approach identified O-GlcNAc transferase (OGT) as a REV-ERBα-interacting protein. By shielding cytoplasmic OGT from proteasomal degradation and favoring OGT activity in the nucleus, REV-ERBα cyclically increased O-GlcNAcylation of multiple cytoplasmic and nuclear proteins as a function of its rhythmically regulated expression, while REV-ERBα ligands mostly affected cytoplasmic OGT activity. We illustrate this finding by showing that REV-ERBα controls OGT-dependent activities of the cytoplasmic protein kinase AKT, an essential relay in insulin signaling, and of ten-of-eleven translocation (TET) enzymes in the nucleus. AKT phosphorylation was inversely correlated to REV-ERBα expression. REV-ERBα enhanced TET activity and DNA hydroxymethylated cytosine (5hmC) levels in the vicinity of REV-ERBα genomic binding sites. As an example, we show that the REV-ERBα/OGT complex modulates SREBP-1c gene expression throughout the fasting/feeding periods by first repressing AKT phosphorylation and by epigenomically priming the Srebf1 promoter for a further rapid response to insulin. Conclusion: REV-ERBα regulates cytoplasmic and nuclear OGT-controlled processes that integrate at the hepatic SREBF1 locus to control basal and insulin-induced expression of the temporally and nutritionally regulated lipogenic SREBP-1c transcript.
O-GlcNAc proteins:
A4D111, POTEF, A5GZ75, AXA2L, P121C, A9Z0R7, EIFCL, C3UMV2, F1JVV5, I6TRR8, MYO1C, IF2B3, DDX3X, TCRG1, OPLA, XPO1, SC16A, SET1A, OGT1, EIF3D, DDX3Y, DHX15, PRP4, SERA, PSMD3, HNRPR, ACTN4, MYO1B, AKAP8, HNRPQ, UGDH, USO1, WDR1, ANR17, GGCT, LX12B, FLNB, PR40A, SF3B1, SPB7, NU155, KRT38, SC24D, GLSK, SC31A, ELP1, SMC2, AGM1, UTS2, BAG4, SC24A, SC24B, AP2A1, LDHA, AL1A1, PGK1, A2MG, CO3, CYTA, KV117, IGHG1, IGHA1, APOE, APOC2, FIBG, TFR1, TRFE, CATA, ALDOA, TBB4A, G3P, HSPB1, RPN1, RPN2, AT1A1, ARGI1, ALDH2, S10A8, ADT2, GELS, ATPB, APOA4, ENOA, PYGL, G6PI, TPM3, PDIA1, CATD, ANXA2, CAN1, TBB5, HS90A, SP1, CO1A2, HS90B, PO2F2, GSTP1, VILI, ANXA4, PARP1, LKHA4, ATX1L, POTEI, UBB, UBC, SAA2, HS71A, HS71B, IGG1, TBA3C, TBA3D, THIO, CH60, BIP, HSP7C, PYGB, PYGM, G6PD, PYC, C1TC, NFH, IMDH2, XRCC6, XRCC5, AT1A3, EF2, PDIA4, P4HA1, ENOB, GFAP, ENPL, IDE, PO2F1, HNRPL, PLAK, DESP, AT2A2, HSP76, DDX5, LEG3, TCPA, RL7, VINC, E2AK2, ITIH2, ANXA7, HNF1A, FILA, CD11B, FLNA, VDAC1, TGM2, PUR2, UBA1, NDKB, TGM1, EST1, SFPQ, SAHH, MCM3, ATPA, PTBP1, SYVC, ABCD3, GRN, TKT, SPB3, AL4A1, PDIA3, KPYR, RPB2, AKT1, PUR9, HNRH1, CASPE, 1433S, S10AB, PRDX2, MCM4, MCM7, HS71L, CTNB1, IRS1, GDE, MYH9, FUS, SPB5, NUP62, TALDO, GRP75, CAPG, TCPZ, STAT3, MDHC, MDHM, ECHA, GARS, SYIC, HUTH, LPPRC, MATR3, MSH2, VDAC2, SYQ, LEG7, COPD, SPB4, TCPE, AL9A1, LMAN1, FMO5, TCPG, SYAC, RBM25, KLK7, DYN2, TCPQ, TCPD, RAB7A, HCFC1, KS6A3, HNRPM, HXK2, CAZA1, NUP98, ACLY, COPB, COPA, SC24C, SYRC, SYYC, UBP14, HSP72, P5CS, XPO2, TERA, MTP, AF17, PSA, HNRH2, EIF3B, SYMC, NU107, EPIPL, TPIS, ACTB, IF4A1, HNRPK, 1433G, PRS4, ACTA, H4, RS27A, RL40, 1433Z, RACK1, ACTG, ACTH, ACTC, ACTS, TBA1B, TBA4A, TBB4B, PRKDC, DCD, VIGLN, CLH1, HNRPU, FABP5, MSHR, EWS, SEMG2, DSG1, SP3, PLOD1, EF1A2, GFPT1, PRDX1, KHDR1, TGM3, DHX9, LG3BP, DSC1, ILF3, TRAP1, PAK2, PSMD2, PABP4, PICAL, PKP1, BLMH, SNTB1, TBB2A, VEZF1, TRI29, UBP2L, LY6D, SRC8, PDIA5, HS902, EPN4, SMC1A, GANAB, MVP, PLEC, NONO, SC23A, SC23B, CDSN, JHD2C, CYTM, DPYL2, PCKGM, TKFC, Q53G76, Q58FF2, Q59EA0, ZN326, FILA2, UBAP2, KPLCE, RBM26, EF1A3, ARID2, TBA3E, POTEE, SBSN, FBX50, Q70T18, Q71E78, TBA1A, SND1, NUP54, MYH14, PEG10, PRP39, TAXB1, CAND1, CARM1, PRSR1, SPA12, ANKH1, ASXL1, NUP93, RDHE2, Q8N6B4, PDPR, TNR6A, COP1, PDC6I, POF1B, ATX2L, DDX1, BAP1, TFG, RBP56, EVPL, DDX17, RENT1, FUBP2, UBP7, NCLN, H2B1A, WNK4, ZC3HA, SCYL1, SPB12, GSDMA, VPS35, PHF12, CIC, STRBP, VAT1, NUP88, ATX2, CPNE1, TCPH, TBA1C, DIDO1, HNRL1, TBB2B, NUP58, ACTBM, TB182, SP130, WNK1, AGO3, MCCB, MOV10, TNR6C, S10AE, DD19A, ATD3A, TBA8, UGGG1, IF2B1, CALL5, RRBP1, NXF1, S2513, PO2F3, AGO2, AGO1, Q9UL79, ACSL5, DD19B, TNR6B, CD11A, EIF3L, SYFA, KLK5, RTCB, WNK2, PKP3, HYOU1, SNX9, COPG1, IF2B2, S23IP
Species: Homo sapiens
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Wang S, Yang F, Petyuk VA, Shukla AK, Monroe ME, Gritsenko MA, Rodland KD, Smith RD, Qian WJ, Gong CX, Liu T. Quantitative proteomics identifies altered O-GlcNAcylation of structural, synaptic and memory-associated proteins in Alzheimer's disease. The Journal of pathology 2017 243(1) 28657654
Abstract:
Protein modification by O-linked β-N-acetylglucosamine (O-GlcNAc) is emerging as an important factor in the pathogenesis of sporadic Alzheimer's disease (AD); however, detailed molecular characterization of this important protein post-translational modification at the proteome level has been highly challenging, owing to its low stoichiometry and labile nature. Herein, we report the most comprehensive, quantitative proteomics analysis for protein O-GlcNAcylation in postmortem human brain tissues with and without AD by the use of isobaric tandem mass tag labelling, chemoenzymatic photocleavage enrichment, and liquid chromatography coupled to mass spectrometry. A total of 1850 O-GlcNAc peptides covering 1094 O-GlcNAcylation sites were identified from 530 proteins in the human brain. One hundred and thirty-one O-GlcNAc peptides covering 81 proteins were altered in AD brains as compared with controls (q < 0.05). Moreover, alteration of O-GlcNAc peptide abundance could be attributed more to O-GlcNAcylation level than to protein level changes. The altered O-GlcNAcylated proteins belong to several structural and functional categories, including synaptic proteins, cytoskeleton proteins, and memory-associated proteins. These findings suggest that dysregulation of O-GlcNAcylation of multiple brain proteins may be involved in the development of sporadic AD. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
O-GlcNAc proteins:
SBNO1, F221A, CNOT1, WIPF3, MYO9A, APBB1, TAF4, P3C2A, DLGP1, C2C2L, DC1I1, CTRO, NCAN, ABLM1, KMT2D, MYPT1, PDZD2, RIMB2, TCPR2, ERC2, ANR28, LAMA5, OGT1, CLOCK, SI1L1, M3K13, HS12A, CP110, MTSS1, M3K7, TPD54, IF4G3, E41L2, FOXO3, KCNQ3, RNF13, MYPT2, AP180, PLIN3, MOT2, MAFK, HCN1, SLIT3, CLAP2, DEPD5, LIPA3, PP6R2, ANR17, LIPA4, NCOR1, GGYF1, HSBP1, ATRN, FLOT1, SYUG, TPPP, TOX4, SRBS2, TOX, ABLM3, AGFG2, RTN3, KCNH1, VAPB, ZFYV9, SC24B, CNOT4, ZMYM6, BAG3, DDAH2, ABL1, CRYAB, LMNA, MBP, FUCO, GCR, G3P, HSPB1, APOD, PERM, IF2A, NFL, NFM, SAP, VIME, CO4A, AN34C, ATX1L, ELFN1, DERPC, CALM1, CALM2, CALM3, LYAG, LAMC1, MTAP2, EPB41, BCR, LAMP1, PABP1, NFH, CO6A2, CO6A3, TPR, SKI, CSPG2, GFAP, KPYM, GNS, ZEP1, ARSB, ITB4, STMN1, ATF7, SYN1, NEUM, EGR1, SON, ELK1, TFE3, CSK22, ICAL, MAG, CSRP1, VDAC1, TENX, CBL, PTPRZ, OMGP, LAMA2, TENA, APC, DNJB2, MAP4, PTPRM, CLIP1, ZEP2, L1CAM, HS71L, CTNB1, ADDA, NU214, NUP62, SYUA, VATA, CUX1, STAT3, PTGDS, GRM5, GRIA1, MATR3, ATRX, NOTC1, MAP1B, SC6A8, PRC2A, UB2R1, NU153, RBP2, GSK3A, TAF6, TOB1, PPT1, FXR2, MECP2, HCFC1, AGFG1, NUP98, ATX1, DSRAD, LAMB2, CAD13, TPD52, STX17, MYPR, CSK21, F193A, SHPS1, IF4G2, PHC1, MAP1A, BASP1, KGD4, FOXK1, PGBM, RHG04, HNRPU, SPTB2, ANK2, NAAA, DYST, NOTC2, TLE2, TLE4, NMDZ1, MEF2C, ZO1, ACK1, LG3BP, DEMA, CAMP2, AHNK, BPTF, CNTN1, ANK3, ROA0, GPS2, MTA1, LSAMP, GAB1, PICAL, ASAH1, RIPK1, KCC2B, BMPR2, VEZF1, UBP2L, GIT2, DPYL1, DCTN1, SRC8, PUM1, EPN4, RRP1B, NCOA6, KCNB1, LASP1, CRYM, NFIX, NUMA1, SHPRH, HECAM, IF4H, PLEC, PTPRR, PTPA, NCOA2, SF01, JHD2C, T22D1, PI5PA, TAB1, NCOA1, ZYX, SYUB, ADRM1, CCDC6, AINX, DPYL2, NTRK2, TBR1, RTN1, RFX7, QSER1, AAK1, QRIC1, MA7D1, TBC25, TB10B, TPRN, FIL1L, SVEP1, GRAP1, AMOT, CCD93, IGS11, ARMX4, NHLC3, PRC2B, SNP47, CE170, ZEP3, SKT, UBAP2, RBM26, AHDC1, VP13D, MRCKA, RPRD2, RN220, F1711, TASO2, MLIP, PAPD7, TENS2, KANK2, CRBG3, ANR40, ABLM2, CAPR2, LIN54, F117B, SCYL2, NFRKB, MDEAS, ZC3HE, LARP1, FIP1, PAMR1, MCAF1, MPRIP, GGYF2, NFXL1, PPR3F, K154L, RAPH1, UB2R2, HAKAI, MTSS2, ASXL2, CEP68, SPT6H, SYT13, MICA3, GRIN1, POGZ, ZFY16, MAVS, EMSY, RBBP6, SH3R1, HUWE1, YTHD3, FLIP1, LYRIC, RIMS1, F124A, LUZP1, PACS2, RLGPB, P66A, KCC1D, AHNK2, NAV3, TEX2, MGAP, CC28A, UBR1, ANKH1, NPAS3, MILK2, ULK2, PHAR4, DCP1B, SPART, CEND, RPTOR, KT222, ZN687, DOCK4, SYNPO, FNBP4, MINK1, OXR1, AVL9, CAMKV, SLAI1, NUP35, REPS2, NBEA, MYRIP, SVIP, PLBL2, NCOA7, TBC15, NEK9, DLG5, GEMI5, WIPF2, F222B, SMAP2, TM263, ZFN2B, LMO7, CTL1, ATX2L, PALLD, CSKI1, MADD, P66B, BAALC, ZCH14, LAR4B, PTPRU, RYR2, TAF4B, SYN2, DDX17, GPKOW, FUBP2, ARHG2, LPP, SNX21, MRTFA, SH3K1, PF21A, ATG2B, PLD4, REPS1, CYFP2, PHIPL, PGCB, PDLI5, MAP6, VCIP1, ZFR, EP400, SPT33, DOCK7, LRRC7, RBM14, NED4L, QKI, SYGP1, LMTK3, PLIN4, ARX, CIC, MED15, KKCC2, MINT, PKP4, ATX2, SH3G3, DPH2, KTNB1, TPPP3, SRBS1, BBS2, YTHD1, WNK3, CFA74, ZCHC2, TB182, AMRA1, ZC12C, SRCN1, SP130, BRD8, WDR13, EPC1, CA198, WNK1, E41L1, ZHX3, VIAAT, Z385D, DOCK5, GORS2, JUPI2, MA6D1, SIAE, PKHA5, RC3H2, TENS1, EMAL4, ZBT20, TANC2, E41LA, APMAP, ARFG3, GEPH, ENTP7, BMP2K, RN146, STAU2, T106B, CARF, TAB2, GGA3, ARHGC, SPN90, DLGP2, CAMP3, PHRF1, PLCE1, STOX2, KANL3, ARP21, S30BP, NRBP, CDC23, GGA2, AKA11, GMEB2, TNIK, PARP4, HCN2, MRTFB, YETS2, EPDR1, NOTC3, SPAT2, SYNRG, G3BP2, BSN, SCAF8, LIMC1, TRAK1, SHAN2, RIMS2, SRRM2, CTND2, JIP1, KCC2A, DLGP4, E41L3, GIT1, WNK2, C2CD2, TLN1, ARIP4, MTCL1, DCAF1, RPGF2, PRC2C, SHAN1, FLVC1, NCOR2, GMEB1, EMIL1, EPN1, NUMBL, M3K4, PCLO, ZHX2, S23IP
Species: Homo sapiens
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Fujiki R, Hashiba W, Sekine H, Yokoyama A, Chikanishi T, Ito S, Imai Y, Kim J, He HH, Igarashi K, Kanno J, Ohtake F, Kitagawa H, Roeder RG, Brown M, Kato S. GlcNAcylation of histone H2B facilitates its monoubiquitination. Nature 2011 480(7378) 22121020
Abstract:
Chromatin reorganization is governed by multiple post-translational modifications of chromosomal proteins and DNA. These histone modifications are reversible, dynamic events that can regulate DNA-driven cellular processes. However, the molecular mechanisms that coordinate histone modification patterns remain largely unknown. In metazoans, reversible protein modification by O-linked N-acetylglucosamine (GlcNAc) is catalysed by two enzymes, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). However, the significance of GlcNAcylation in chromatin reorganization remains elusive. Here we report that histone H2B is GlcNAcylated at residue S112 by OGT in vitro and in living cells. Histone GlcNAcylation fluctuated in response to extracellular glucose through the hexosamine biosynthesis pathway (HBP). H2B S112 GlcNAcylation promotes K120 monoubiquitination, in which the GlcNAc moiety can serve as an anchor for a histone H2B ubiquitin ligase. H2B S112 GlcNAc was localized to euchromatic areas on fly polytene chromosomes. In a genome-wide analysis, H2B S112 GlcNAcylation sites were observed widely distributed over chromosomes including transcribed gene loci, with some sites co-localizing with H2B K120 monoubiquitination. These findings suggest that H2B S112 GlcNAcylation is a histone modification that facilitates H2BK120 monoubiquitination, presumably for transcriptional activation.
O-GlcNAc proteins:
A4D0Y7, A4D111, A4D1Q6, A4D1R6, TBAL3, IMA8, HAX1, IMA4, IMA3, HNRDL, XPO1, P4HA2, NUP42, HNRPR, PPIH, CPSF5, HNRPQ, IMA7, HNRC1, PR40A, BAF, U520, NU155, RL1D1, AP2A2, K2C75, LMNA, VTNC, K2C1, HSPB1, H2A1B, RLA1, RLA2, RLA0, K1C18, K2C8, NPM, PDIA1, HNRPC, ODPA, VIME, RS17, K2C7, ROA1, H2AZ, CH60, BIP, HSP7C, PABP1, K1C13, P4HA1, TRI27, FOLR1, RS2, H13, HSP76, RL7, RL17, NUCL, LMNB1, FBRL, ROA2, SFPQ, RS3, H2B1O, RS12, ATPA, U2AF2, RL13, RBMS1, RL12, HNRH1, RL9, HS71L, RL22, NU214, RL4, NUP62, RBMX, GRP75, IF4A3, RS19, RL3, LAP2A, LAP2B, RS27, MATR3, RL27A, RL5, RL21, RS9, RS5, EFTU, RBP2, FXR1, FXR2, NDUA8, ROA3, HNRPM, IMA1, HNRPF, NUP98, HSP72, SEC13, NH2L1, HNRH2, NU107, ACTB, RS3A, RL27, RL37A, RS7, RS16, RS14, RS23, RS13, RUXE, RUXF, SMD1, SMD2, SMD3, RL7A, RS4X, H4, H2B1C, RAN, RL23, RS15, RL30, RL31, RL32, RL11, RL8, TRA2B, EF1A1, RAE1L, ERH, RL19, SRSF3, H33, HNRPU, U2AF1, TIAR, H11, RL18A, RL6, K1C17, SSBP, CSTF1, RL18, KHDR1, SRSF1, DHX9, NCBP1, NU160, SF3A3, ILF3, CSTF3, TADBP, ROA0, SRSF6, G3BP1, PABP4, SF3B2, SPTN1, HNRPD, UBP2L, PUM1, IMB1, U5S1, PDIA6, PLEC, NONO, RCN1, SF3B3, SF3B4, SF3A2, RBMS2, SF3A1, SF01, ELAV1, SRSF7, SMU1, NU188, UBAP2, PRP8, NUP54, K1C28, LYRIC, NUP43, NUP37, NUP35, SMRC2, PUM2, Q8TEA6, PO210, NU133, PRP31, TFG, FUBP2, TNPO1, LRC59, MSI2H, SNR40, SEH1, FUBP3, ZFR, RBM14, STRBP, NUP88, ROAA, EBP2, DDX50, TBA1C, HNRL1, NUP58, NUP85, XRN2, CSTFT, RPF2, NCOA5, NXT2, DDX21, Q9P0H6, DJB11, NXF1, PUF60, MRT4, NXT1, NUP50, PRP19, G3BP2, YBOX2, LSM2, RM11, RL36
Species: Homo sapiens
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