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Lee SJ, Lee DE, Choi SY, Kwon OS. OSMI-1 Enhances TRAIL-Induced Apoptosis through ER Stress and NF-κB Signaling in Colon Cancer Cells. International journal of molecular sciences 2021 22(20) 34681736
Abstract:
Levels of O-GlcNAc transferase (OGT) and hyper-O-GlcNAcylation expression levels are associated with cancer pathogenesis. This study aimed to find conditions that maximize the therapeutic effect of cancer and minimize tissue damage by combining an OGT inhibitor (OSMI-1) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). We found that OSMI-1 treatment in HCT116 human colon cancer cells has a potent synergistic effect on TRAIL-induced apoptosis signaling. Interestingly, OSMI-1 significantly increased TRAIL-mediated apoptosis by increasing the expression of the cell surface receptor DR5. ROS-induced endoplasmic reticulum (ER) stress by OSMI-1 not only upregulated CHOP-DR5 signaling but also activated Jun-N-terminal kinase (JNK), resulting in a decrease in Bcl2 and the release of cytochrome c from mitochondria. TRAIL induced the activation of NF-κB and played a role in resistance as an antiapoptotic factor. During this process, O-GlcNAcylation of IκB kinase (IKK) and IκBα degradation occurred, followed by translocation of p65 into the nucleus. However, combination treatment with OSMI-1 counteracted the effect of TRAIL-mediated NF-κB signaling, resulting in a more synergistic effect on apoptosis. Therefore, the combined treatment of OSMI-1 and TRAIL synergistically increased TRAIL-induced apoptosis through caspase-8 activation. Conclusively, OSMI-1 potentially sensitizes TRAIL-induced cell death in HCT116 cells through the blockade of NF-κB signaling and activation of apoptosis through ER stress response.
O-GlcNAc proteins:
IKKB
Species: Homo sapiens
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Sun QH, Wang YS, Liu G, Zhou HL, Jian YP, Liu MD, Zhang D, Ding Q, Zhao RX, Chen JF, Li YN, Liang J, Li YL, Quan CS, Xu ZX. Enhanced O-linked Glcnacylation in Crohn's disease promotes intestinal inflammation. EBioMedicine 2020 53 32114385
Abstract:
Treatment of Crohn's disease (CD) remains to be a challenge due to limited insights for its pathogenesis. We aimed to determine the role of O-Linked β-N-acetylglucosamine (O-GlcNAc) in the development of CD and evaluate therapeutic effects of O-GlcNAc inhibitors on CD.
O-GlcNAc proteins:
IKKB, TF65
Species: Homo sapiens
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Huo B, Zhang W, Zhao X, Dong H, Yu Y, Wang J, Qian X, Qin W. A triarylphosphine-trimethylpiperidine reagent for the one-step derivatization and enrichment of protein post-translational modifications and identification by mass spectrometry. Chemical communications (Cambridge, England) 2018 54(98) 30379171
Abstract:
We report a new reagent that is capable of both chemical derivatization and selective enrichment of azide-labeled PTM peptides for sensitive identification by mass spectrometry (MS). Facile sample recovery, enhanced ionization and fragmentation in MS of the enriched PTM peptides are achieved, which leads to the identification of 3293 O-GlcNAc peptides and the location of 1706 sites in HeLa cells and efficiently expands the current mapping scale.
O-GlcNAc proteins:
MEIKN, BLT3B, SHOT1, TTC24, PIPSL, HFM1, ZN320, NBAS, CQ102, VWA8, SBNO1, Z804B, CC14C, SH321, EFCB5, XIRP2, ODAD3, CNOT1, BDP1, ANR62, CC88B, AN33B, NKX26, PGP, F186A, ARRD5, FBP12, ANKUB, CI092, CE052, FA47D, SMHD1, LRIQ4, GLOD5, ZN233, SH2D7, MARHB, TTLL8, ABTB3, A30BL, ZSWM8, P121C, ERI2, PP2D1, CEA18, R212B, YV023, ZN727, VGLL3, YD021, RUXGL, IQAK1, MAGBH, FOXO6, FHAD1, SRRM5, ZN879, S14L6, CJ142, KRBX1, MCRI1, FONG, CE067, F227A, CRCC2, KIF2A, MYO1C, EYA2, AP3B1, SPT5H, TAF4, HIP1, CDC7, ST1C2, WASL, IPO5, EMAL1, P3C2A, EXOC5, PSDE, USP9Y, BCL9, CAC1A, PITM1, MPP10, TRI38, NDKM, ARI1A, NCKP5, FCHO1, SOCS3, TRAD1, RHG33, TYB4Y, UTY, ENC1, ZN197, APAF, TERT, CHK1, GNB5, TCRG1, UN13B, RASM, PPE1, IFIT3, IKKB, TIM23, HGS, AURKA, MYPT1, XPO1, IPP2C, ZN646, PDZD2, SPTN2, SET1A, TRNK1, PER2, SYNJ2, ZN536, IKKA, TBX3, ARPC2, TBXT, VILL, NKRF, ZN185, CASC3, CLIC2, ACOX3, NPHP1, OGT1, PPM1D, RA51B, SHIP2, EIF3D, IPO8, MSH4, MAGB4, ARPC5, PER1, ZSC9, ZZEF1, TET3, SI1L1, PRP4, SERA, IRAK2, PSMD3, TEX33, AP5Z1, MTSS1, PAX4, WDR62, PRPF3, SYNJ1, IF4G3, KCAB3, E41L2, FOXO3, TGM5, SYT7, PPIP1, CHM2A, PLRG1, LDB2, BUB1, HTSF1, STX6, ENSA, CPSF5, CREB3, AK1BA, KALRN, MYPT2, MED14, SOX15, KLK8, PRKN, SMCA5, ZC3H1, TYW4, LZTS3, GANP, KIF1B, PHLP1, ZN861, BRNP1, MPZL2, OGA, VINEX, HNRPQ, RNBP6, GMDS, REV3L, JAK2, MAFK, MUSC, CTND1, HPGDS, Z354A, RT14, PQBP1, BRD4, ABCB7, PLCH2, SRGP2, DEN4B, N4BP1, ROCK2, COBL, CPNE3, ZBED4, LIPA3, OBSL1, BRE1B, PHF2, ZC11A, CLU, DJC13, ANR17, SIN3B, LIPA2, LIPA4, ZN253, ZN217, FLNB, NCOR1, NDUS6, RM33, DPOLQ, CDC45, MPPB, USH2A, SRS10, GEMI, ECI2, TAF5L, ZN821, DAB1, MYCB2, U520, OFD1, UTP20, NU155, S2512, PALM, ZN189, CCNK, SERF1, PIAS1, DNJC8, RAD17, ANXA9, CLPX, SEGN, CDKL5, NEBL, S14L2, RECQ4, RECQ5, RMP, AL1A2, TOM70, TOX4, MICA2, K0754, FCSD2, SRBS2, SASH1, CSCL1, LRIG2, SUN1, PRP6, PCF11, KDM4B, CE152, SOX30, UBR5, REC8, DUS14, NDUB8, KLHL2, LETM1, MBD4, KAT7, KCNH1, SMC2, IPO7, SLU7, SVIL, NPT2B, LCA5L, FMNL1, PCNT, CNOT4, CPSF4, NFAC1, EYA4, BRD1, HERC2, HS74L, RIGI, ZMYM6, BAG3, DCMC, DDAH2, TGM3L, TBX18, TBX6, BCL10, APBA3, NSD2, GSHR, CRYAB, LMNA, SPTA1, ESR1, ANGI, TDT, CYTB, GCR, SODM, MYCN, G3P, P53, HSPB1, ARGI1, PCCB, RLA2, RLA0, RPC4, K1C18, FYN, NFL, NFM, PERT, CRGC, SYEP, ANXA6, RHOC, GLI1, PFKAM, CATG, INHBA, VIME, ANXA5, SNRPA, VILI, CN37, HMOX1, DLDH, HXB7, DPOLA, IFIT2, WEE2, FBSP1, BNIP5, AN34C, ACSM4, PRR29, F90AO, YT014, R10B1, GRL1A, F200B, DERPC, CTF8, ZN888, RGPD2, GIMD1, ZN728, CH088, AT8OS, MYBA, ARAF, ODP2, KAP0, HEM4, HSP7C, SPTB1, TOP2A, VDR, DMD, ADHX, NFH, TPR, ANXA3, SKIL, NR2C1, HXD8, ENOB, T2FB, MTDC, 3BHS1, GFAP, KPYM, HXB1, PO2F1, ERF3A, EZRI, PHKG2, DESP, ANK1, NCPR, CBPE, PLCG2, ZFX, ZNF14, ZN708, ZNF17, ZNF19, ZNF20, ZKSC1, ZNF28, ZNF30, ZSC20, ZNF7, KPCA, UBF1, ATF7, DDX5, LOX12, EGR1, ARY1, SON, ATF1, ATF6A, NUCL, HXK1, TNNI3, HME2, SL9A1, RAB3B, LMNB1, GRAH, NEBU, AOFA, ZNF10, TGM2, MUTA, PERL, ROA2, CBL, KAPCB, HEMH, XPA, CRCM, SAHH, IF4B, PAX7, GATA2, CPT2, RIR1, EF1B, CCNC, DNJB2, PSA1, MOES, DDX6, RAE2, PTBP1, SYVC, 1433T, ARNT, RFA1, MAP4, PSB9, TMOD1, ITPI2, HXD9, ERCC5, EPHB2, PTN6, SHC1, KDM5A, LMOD1, TYK2, PRDX6, CDC27, WEE1, MPIP1, MPIP2, NKTR, CLIP1, RPB2, KAP1, CPSM, ZEP2, CASPE, 1433B, STIP1, FOXN2, TF2H1, C2TA, LSP1, DUT, GCYA2, MCM7, HYES, MPI, CTNA1, NOS2, SPB6, MERL, RFC4, RFC1, ADML, RORA, CBS, GDE, ACTN2, ADDB, NU214, DEK, CYLC1, ATP7B, SOX5, SOX11, ZNF93, VATE1, 8ODP, LONM, PGM1, GNL1, PEDF, ODO2, SRP14, IF4A3, SMBP2, CUX1, TYRP2, MLH1, STAT3, UBP8, PEX19, ECHA, ETV6, STAT6, AF9, HELZ, LPPRC, HD, ECE1, MUC18, BTD, MAGB1, KSYK, UBP5, KI67, KPB2, KPB1, RECQ1, IF2M, BRCC3, RL28, MAP1B, NEDD4, UTRN, CAPZB, CDX1, RL29, UCRI, PPCE, RFX5, PI42A, RXRG, NRIP1, PRC2A, CCN3, AL9A1, NASP, RM19, CENPF, MCM2, YLPM1, VPS41, NUMB, CLK1, NU153, RBP2, RGS3, RGS7, TSC2, TAF6, DNLI3, ETV1, DYN2, TUB, TCPD, PAPOA, PLCD1, ZNF80, ZNF81, ZNF84, BRCA2, RENBP, MECP2, SSDH, AFF2, AFF3, MYOM1, HNRPM, NCBP2, MP2K6, GDIR2, AGFG1, ZN135, ZN142, ZN143, RBM5, SPSY, HXK2, DGKQ, THOP1, TXTP, PPP5, LIMK2, SMTN, DPOG1, ICLN, BLM, PDE1A, GALC, KAD2, IF5, NR1H2, AFAD, AF17, ADK, DSRAD, UCP3, DLX1, SYMC, ATP5I, HDAC4, PEX3, PER3, RP1, SIK1, PRD15, UBS3A, NAC3, NU107, SNX16, RGS8, FBXW4, SESN2, TIRAP, H2B1D, CU082, MCCD1, EIF3E, PTEN, IF4A1, SNP25, DEST, ARP2, ISL1, REC21, STXB1, 1433G, UBP46, TIM10, PRS4, PRS10, ERF1, GAK8, RS4X, RBX1, TRA2B, ACTG, F193A, NOP14, RBM6, GTF2I, DLG4, IRX6, GSTO1, RELN, PRKDC, ELF3, MAP1A, SIM1, SSBP2, TMF1, RT05, RT11, RT09, HMGN5, SKOR1, FOXK1, PRR5, DAB2, EFNB1, RBM10, RBM3, VIGLN, BORG5, FANCC, CLH1, HSF1, MYPC1, U2AF1, SPTB2, TIAR, SET, FOXK2, RELB, AMPD2, ANK2, TFAP4, XPC, OCRL, AK17A, MEF2B, SP2, CENPE, KIF23, MMSA, ID2, ZNF45, APBA1, HEN1, FKBP4, RL6, TOP2B, DYST, KMT2A, CENPC, ERCC6, TAP1, ZN117, ARI5A, IF4G1, TLE4, UBE3A, DYN1, SRS11, CALD1, RN5A, EMAL5, BTK, EXOS9, MTG8, GABPA, CDK18, ZO1, TRHY, PDE4B, SPAG1, KHDR1, DPOE1, SRSF4, GOGA3, PDE4C, DEMA, PDE4D, RBL2, ZN844, ACSM1, DMWD, EP300, AHNK, ZNFS1, FCHO2, PLCX2, DYH14, K2012, CGNL1, CF210, FP100, MESP2, NEXN, CPSF1, MPPA, SCRN1, TF3C1, HYAL1, BPTF, SFSWA, SF3A3, DPYD, TP53B, IFRD2, ILF3, EPS8, FOXC1, ANK3, GNDS, SEC20, NFX1, TIAM1, AF1Q, AKAP6, PRDM2, CAF1A, TRAF3, AIMP2, CBX3, DDX10, TBX2, ERCC8, GPS2, SBP1, NMI, PABP4, CD5R2, PPIL2, MB211, PM2P3, ORC1, ORC2, SNTB2, PPIG, FKBP5, MYO9B, GAB1, BIRC2, PICAL, SQSTM, BFSP2, PRP4K, ATR, SNW1, IQGA2, MTMR1, CUL4B, ASPP2, DYR1A, PTC1, RAB32, FHL1, FHL3, PM2PB, CAC1S, THOC5, NCOA4, SPTN1, KCNC3, CDK13, CKAP5, CYLC2, DAG1, SRTD2, MORC3, SAFB2, UBP2L, SCRIB, DOC2B, DOCK1, BTG3, ZMYM3, DYHC1, EI2BA, SRC8, FAK2, FLNC, FA50A, GRB14, HES1, NF2L1, FAT1, DHX8, MCM6, ITPR3, ZN266, ZN235, ZN460, PLSI, PUM1, KANK1, MELK, SMC1A, RRP1B, NCOA6, GSE1, PSF1, BMS1, LBR, STAT4, CBX2, KIF22, MEF2D, MTF1, MYPC3, NC2A, NFIX, ZN638, NOLC1, NR1D2, PSME4, CUL7, SLMAP, GAPD1, FRPD4, CND2, MO4L2, SUZ12, R3HD1, SNX17, S39AE, LRC14, DPOD3, IF4H, KIF14, EEA1, CD5R1, NCF4, PLCL1, PDK1, PLCB4, PLEC, PTPRR, PWP2, IRF4, ZMY11, L2GL1, UBE3C, PUM3, DLGP5, RBY1F, KS6A1, SAFB1, SYCP1, PP1R7, SP17, MED22, TAF1C, NCOA2, TRIPB, PCH2, MED1, JHD2C, ZN174, DLG2, CEBPE, TAB1, STXB2, ZFHX3, ZBTB6, ZYX, SEPT7, ADRM1, AINX, PSMD5, PKN2, TAF12, CDC37, B2LA1, TAF9, MAPK3, TBR1, CP1B1, DGKD, THTR, PCKGM, ZN827, LONF1, EX3L4, TPRXL, GEN, HNRL2, LONF2, SAMTR, PDS5A, MOONR, QSER1, WASC4, EX3L2, TECT1, ERC6L, RGPA2, D19L1, ZXDC, CCD57, PWP3A, ATG2A, FHOD3, IF2GL, KLH38, HFE, BTBDG, LRRF1, RFX4, LRRK1, F161A, INAVA, MA7D1, PKHG6, CHD9, TBC25, C144B, OD3L2, ZN718, AL1L2, P12L1, PTHB1, GON4L, GRDN, GVQW3, PAR14, CP100, ZN404, CL036, SPAS1, SV2C, YJ016, ZFP69, CE022, C2CD3, KMT5B, LARP7, HYDIN, KCD21, IQCC, PLCH1, FIL1L, ARI4B, GRAP1, Z658B, PAP1L, TIGD2, FNDC1, VWA3B, PAN2, CN177, Z585B, SBK1, UBP39, TYW2, FAKD1, CTSRT, SGO2, CC178, ODFP2, CAVN4, FSIP2, UROL1, ZN628, TRI61, ESCO1, ZN789, BCORL, ZMAT1, PP6R3, DCA17, FSCB, BRD10, ZC12B, NHSL2, ZN831, AKAP4, MTUS2, FA47A, MEIG1, PRC2B, RRP12, IQEC2, SPIN3, ZN506, DOP1, F209B, GASP1, DGKK, CYTSB, CD158, SPXN4, FBX47, TCHL1, TDIF2, ERIC3, LRRK2, SAPC1, CE170, PR15B, CJ055, SNPC4, CTSRE, NHSL1, F120S, C2D1B, TEX35, FA83B, SYRM, AXDN1, FKB15, AKND1, ZC3HD, MPP7, UBR4, ZN684, SWT1, SKT, CC183, RHG21, BEND3, UBAP2, PHF19, LITD1, F27D1, TSTD2, ER6L2, PPR26, ACBD5, UT14C, TUT4, DEP1A, CE162, FRY, ZBT37, MAGI3, KAD9, DDI2, MEI1, CC181, LIN9, ZN658, CROCC, CBPC2, MCAF2, RIF1, ZN468, SPXN1, OBSCN, NTM2D, CE350, RPRD2, SYDE2, KLD7A, BRE1A, MYOME, P210L, ZN318, A20A3, ZN691, PPRC1, SPO16, MYSM1, NTM1B, TAF3, SNX30, TASO2, KHDR2, ECM29, NAA35, MBNL2, OBI1, USPL1, F219B, RN123, FBX31, FBW10, ZKSC2, RN213, WDR25, CP135, Z385C, AR6P4, ARID2, TENS3, SPT2, FMN1, ANKS6, USF3, MSL1, S31H1, CRBG3, FRPD2, RHG17, DUS29, C19L1, VIR, CYTSA, ZN660, REP15, BLT3A, SP5, CARL2, K0930, JADE1, SNR48, CAPR2, SPOPL, CCSAP, PKHA7, ADNP2, IF5AL, GRHL2, ZN425, ACD10, IFIX, NIPBL, LIN54, R7BP, TET2, TEN4, Z280D, NAA16, RADX, SANBR, ZSC25, SCMC1, ACSM5, JHY, CRCDL, SWAP1, ZN774, ZN544, JMJD6, CAVN1, FXL22, M18BP, CDC73, T2H2L, XRRA1, TTC41, NEK5, NFRKB, LMOD2, RL22L, PKN3, ERIC5, ANR16, FXL19, ZN880, TM10B, KLH35, PSRC1, BORA, IYD1, KCD18, GASP3, FBX38, FOXR1, ARMD1, BRAT1, ZC3HE, LARP1, ATAD2, SPG17, RICTR, BRWD3, TSSK4, F111B, SAMD1, SARM1, KLH17, PADI6, C1TM, ANR12, ANR11, FIP1, SAS6, UD2A3, CWC27, LRIG3, MIC27, BI2L2, MCAF1, BCOR, MPRIP, ZY11A, NSMF, RBMS3, RPTN, DNMBP, GGYF2, CCNI2, ZN782, EMAL6, SYNE3, MASTR, CU136, MEX3B, ZNF66, ZN793, LN28B, CCD81, RN111, ZN704, BICL1, CC141, WDR87, ZN493, CO039, CCD73, SRCAP, ZN662, NBEL1, YD022, SHSA6, YO027, YJ005, TSH1, CBAR2, CG065, MSD1, K0408, CFA65, UBN2, BEND4, F205A, RHG27, FRMD7, FOXNB, RFX8, FGD6, ANKS3, YS043, VP13C, UBP34, UBP31, UBP53, UBP43, ZN365, CEFIP, CENPU, SSH2, CEP68, SPT6H, RUFY3, ERIP6, DHX30, ZN765, MCM10, DOK3, GDPD3, RFIP2, FAKD5, OTU6A, ZN627, KDM3B, STRAA, MICA3, OTOP3, SSX7, U17L1, H2BWT, ZCCHV, GVIN1, TICRR, EFL1, PBIR2, SETX, KANL1, NUP54, PRIC2, ZN572, RGPD4, POGZ, ZFY16, MYCPP, TMC6, NUFP2, MAVS, CLAP1, DHX29, LIMS2, TT21B, HEAT3, CFA91, ZN438, HDGR2, EMSY, AKNA, RAI1, ANKAR, I2BP2, AB12B, SNX20, SPRE1, RBBP6, ANS1B, UBE3D, PTAR1, TCPR1, RABEK, HUWE1, YTHD3, FLIP1, TAF8, KHDC4, VP13B, S1A7A, PHLB2, CROL1, KAISO, ZN605, UBP37, K1328, RN180, PATL1, MYPN, PEG10, ATG4D, TTC7B, ISCA2, PABP2, LDB1, PB1, RIP, MARH3, NFE4, RIMS1, CATAC, NT5D3, CASZ1, VASH2, LUZP1, MORC1, MYPOP, NRAP, IQGA3, ZCH18, PACS2, MON1A, TSYL5, ZSC30, PARG, LIPB1, LONP2, RASF3, NLRC5, CHD1L, SKAP1, AROS, CDR2L, DAA11, EZHIP, CQ082, CIR1, HTR5A, ZFAN4, SNX32, HOGA1, DRC11, ZN761, GOLI, TRI50, Z354C, CD20B, KMT5C, ZN573, PRGC2, P66A, RASL3, MD12L, I2BP1, RB6I2, RIOX2, MY18B, RBM45, SIAH1, RELL1, LACC1, HID1, ANKY2, PSTK, VRK3, CROL2, PKHH2, AHNK2, TIAM2, AN18A, FMNL3, SAM9L, NAV3, NAV2, CCD50, FABD, MISP, HERC6, WDR75, MFN1, CCD60, TEX14, MA7D3, NXP20, CCD83, DNAI3, MGAP, GCC2, RP1L1, BRSK2, Z3H7A, TPH2, UBR2, ANKH1, SUGP1, SUGP2, KIBRA, GOR, CCAR1, SLF2, RM41, GPAM1, KLHL7, ETKMT, DDIAS, RB12B, ZC3H3, SMC5, DHX37, KBTB2, SPB1, NIM1, C144C, CKP2L, IHO1, SUV3, ERF3B, FANCM, ZZZ3, EXOC8, CF206, P20D2, DAAF8, CFA46, SAXO1, SACDR, RTKN2, SAM14, KMT2E, DOCK3, ABI1, ASPM, F185A, CA087, IQCK, SPG16, SPART, SPICE, TTC5, TAGAP, RPTOR, EID3, AHI1, ZN567, ZN687, REXO1, S6OS1, CRBG2, THEM5, ANR35, CLASR, AN36B, RUSC2, CF223, RHG18, PARP8, EH1L1, METL4, CMYA5, VPS8, PALS1, SYNPO, FNBP4, RDHE2, PRS35, PGBD5, NIN, SPA6L, SPEM1, TT30B, LRC71, AF1L2, CERS5, SRBD1, TAB3, MACOI, MINY1, CCD33, TM148, ESX1, PACRL, TRIMM, TM217, ZN676, NANG2, ANR31, CNTD1, TEANC, ZN615, K1958, ENAH, CDYL2, CO056, ZN709, JMY, ZN454, ZN565, YV006, SR1IP, CDRT4, TAC2N, GAR2, FSIP1, ZN383, PNDC1, FA47B, MARHA, KBTB3, CI106, CAST3, ZBT38, CH058, SMYD1, UN13C, KY, CK072, ZN114, SERB1, HJURP, SEN2, GLBL3, MACA2, SMG8, RN214, Z280C, MROH1, PAPD5, CC168, ICA1L, EHBP1, CBPC5, RB15B, SMC1B, PHC3, BEND2, SIMC1, NSUN7, SRFB1, DDHD1, SP20H, CBPC3, ARMC2, PDZD8, ZN555, RTL9, DP13B, NAV1, WDR19, KMT2C, FBX22, SYNE1, BD1L1, FAD1, FLCN, PXT1, DBF4B, IPMK, ABHDB, DMBX1, FBH1, PJA1, KNL1, NEK11, KDM2B, ARK74, CLHC1, CFA61, NEDD1, RLA0L, ZFP28, THOC2, INADL, KI18A, ZNT5, SNIP1, WDR48, UHMK1, NEIL3, FA76A, ZN671, PRR7, PUM2, KLDC4, NANP, AT2L1, RBM46, PMFBP, CC110, ZN502, TBC15, ZN596, GAR3, FANK1, ZN507, PHOP1, ALMS1, DC2L1, CHD6, HUMMR, SP7, ACTT1, HELQ, DMXL2, DLG5, MIPT3, OTU7A, S26A7, ATS17, S3TC1, TBCK, PO210, CE192, GEMI5, FBF1, RPGF6, SMCR8, PARD3, PNISR, ZN483, DI3L1, ZN526, GIPC2, CP078, DUS19, THAP3, ZDHC1, TB22A, PDC6I, CO040, DCAF4, MITD1, TFB1M, TPC14, DC2I1, UBCP1, TRUB1, LMO7, CKAP2, CCNB3, ATX2L, PHIP, RT4I1, PALLD, CRGN, SYNE2, CNKR2, ASB10, ACO11, P66B, ASB17, BBX, CTBL1, ELYS, TITIN, TRIB2, SMG7, RTF1, IP6K1, PHYIP, DCNL4, P55G, NR4A3, PHF3, NDRG1, HS105, ZN592, PRP16, ANS1A, FAN, AKAP1, ZN75C, CENPI, PRCC, RREB1, HDAC2, DPF1, DPF3, REQU, CBP, SYMPK, HYAS2, KAT2A, RPGR, DDX17, KIFA3, NEO1, RAD50, RAB8B, ARHG2, IRF7, TF3B, DVL3, USP9X, CUL5, LPP, TP4A1, HGD, SMCE1, FBXW7, FBX32, TOP1M, TRI63, LMBL2, ZN622, 5NT3B, FBXW5, PSMG2, TEKT1, FAKD4, TET5B, C102A, RM24, SPSB4, ZUP1, CC74A, TTC28, R51A1, DACT3, SH3K1, PF21A, ELMO3, PINX1, CC049, S1PBP, ZN775, DOC10, ATG2B, ZBTB9, ROP1L, COAC, CHM4C, CC124, OPTN, S7A6O, GASP2, RMD1, OTUB2, ATG4C, DRC10, MTBP, RRFM, MTEF3, ELP4, HOOK2, MTMR8, ZN837, RL39L, MITOK, SGF29, RBM33, DTBP1, ZN503, ELMD3, THOC1, HMCES, IMP4, KLD7B, SCMH1, TOE1, MSD3, ZCCHL, TONSL, NTAQ1, PDLI5, PRR11, FMC1, C2AIL, INT4, SYNM, REXO5, GMPPA, GMCL1, ZN496, NGLY1, RBM41, TPD55, ESIP1, MAP6, ZN594, ZN469, ZN462, FEM1C, PGBD1, ZN521, TOPK, PRAC1, COX42, KCNS1, Z512B, ZFR, F167A, P12L2, CD036, NSD1, EP400, IFT74, SGCZ, CX058, CEP19, CH048, CL037, MRFL, Z354B, PRIPO, RMD2, CJ090, IFAS1, TEKT5, TEX55, FEAS2, CCDC7, CFA53, ZN512, CQ10A, NSE2, CE034, RIPR3, TEAN2, ZSWM3, YTDC1, ZNF48, F161B, F218A, TTC14, CK037, ZN578, PWP2A, DOCK7, ZN641, ZN582, ZFP3, LRRC7, BIRC8, INP4A, TSSK2, RBM14, ADCYA, IPP2L, ZN317, PNMA5, K1908, FMNL2, PUS7, F111A, PLIN4, SMG1, ALKB3, KI20B, RHG07, ATAD5, TEFM, RAB3I, GCNA, PRAM, MAGI1, RET7, PANX2, MED15, ERBIN, TRIB1, HMCN1, CRML, PRR25, LYSM1, CCNL2, SMC6, ZN607, ZN587, IWS1, SEBP2, RSF1, RUFY1, IMP2L, MINT, SETB2, ACOX2, AGAP2, EYA3, DNJC2, MPP9, M3K14, S10AD, SCAFB, ELF4, KLF6, PHB2, CHP1, KIF2C, LYST, ATX2, SMAD5, BARD1, NPAS1, EPAS1, TS101, CPNE1, SMO, EBP2, PKP2, AKAP9, ARP5L, SIN1, RNZ2, CMS1, SENP7, SLF1, COE4, ST4A1, ZSWM1, COR1B, LSMD1, SRSF8, PYGO2, FSP1, GPTC1, LLPH, SIKE1, TRI56, ZPBP1, BTBDA, TACO1, PIMRE, S2533, HAUS8, ALKB7, DIDO1, MTA3, DCNL5, RAMAC, FAP24, LRRC1, MED18, RCAF1, SCMC3, THUM3, CP250, KTNB1, PHF20, RUSC1, RIOK2, TIM21, KIFC1, HIRP3, TRAIP, FUND2, CYREN, CDCA7, MND1, CAR10, NADAP, GATA5, SYCP2, FANCJ, SRBS1, CARD6, ZN471, OSB10, RFIP5, SPZ1, CAR14, CAR11, T121B, TGT, TDRD1, TEX15, RNF17, STK31, UBP26, OSBL1, FACD2, AN30A, MAK16, SCAPE, DGC6L, RTF2, PECR, LRRC3, RNF26, SCOT2, RM01, ACE2, MSTRO, HYCCI, YTHD1, LRRC2, NEUL, PBX4, BCDO2, CEP41, SETD2, TBD2A, LDH6B, PANK2, NSD3, NUF2, PUS3, BARH1, OSBL7, UACA, REN3B, NIBA1, UBXN6, TRI15, TRIM4, F117A, SPEF2, LRCC1, ZFHX2, CFA74, AMRA1, CE295, ZY11B, TANC1, XPO4, GRIP2, ASXL3, CEP44, ZN407, SRCN1, CCSE1, WDR33, TGIF2, ROGDI, REXO4, NXF2, MFF, DRC3, CLPB, LSG1, NUAK2, NAT10, IQCN, ILKAP, SP130, UBP44, BRD8, RGAP1, PUS7L, ZCPW1, GZF1, BC11A, I2BPL, ISCU, RSPH9, VPS11, AL8A1, TARA, EPC1, CI037, PDCL3, ADNP, TNMD, RBP17, IPYR2, MIXL1, HIPK2, ZN106, E41LB, UBQL3, YI012, MOD5, GHITM, BOLA2, BORG4, UN45A, DSN1, CA198, RBSK, FN3K, WNK1, PLK3, E41L1, EMRE, PRD12, ZN644, VIAAT, THAP9, BICC1, CCD86, MYH16, CIAO3, ACSS3, BCAS3, ZN552, ASB8, SH24A, SMYD3, MB12B, ZN665, CCSE2, ZN430, NOL11, PAAT, MINY3, ECT2, F204A, CF208, ANKZ1, GHC1, PPIP2, MARH7, CNO10, SPE39, ANRA2, UNKL, RPF1, RPA2, SYCM, NMNA1, MLXIP, RENT2, BRF2, CLSPN, BCDO1, PRD16, PKHA1, AS3MT, TENS1, NMRL1, SPC25, TAF9B, Z286A, TPC, MRM3, GPBL1, CENPJ, ZBT20, HES4, NCOA5, TANC2, ZN532, SYTL2, MAGE1, K1586, ZSWM6, ZDBF2, CHD8, GPAT1, FBSL, ZN304, NDF4, HMX1, S40A1, GCM1, VTA1, EXOS4, UBN1, MKKS, MED4, SCRT2, CK016, PLCB1, A1CF, DDX4, DMRT3, INCE, PRDM9, BIN3, ENTP7, BIRC6, PDLI7, ACSA, DYRK4, ANM8, ASH1L, KLHL1, TSH2, SMYD2, SNRK, TBG2, STRN4, ZN277, LATS2, C42S1, PNO1, TOPRS, MBIP1, RAD18, HOME2, SALL1, ZN275, BRWD1, KLC4, AT8A2, DEPP1, CTSRZ, ZF64B, ECHD1, RBM12, ANKE1, MDN1, UFSP2, MITOS, OTULL, TYDP1, POTE1, DCA13, NUD15, RN19A, TYW1, EXOC1, UQCC1, MED17, TBC13, DJC11, INT7, FANCI, INT13, DZAN1, FAIM1, INT10, KTU, TBCC1, RPC2, RBM28, RBM22, BSDC1, WDR70, SLTM, SMOX, PIHD1, PARI, RMND1, BABA1, THG1, HPF1, IRAK4, TXN4B, NDUBB, MARH5, SYBU, MTMRA, TEX10, CNTLN, TRM1, CARF, NSE4A, DDX43, DPP3, ETAA1, ABI2, DYH9, HXC10, DACT1, FA53C, BCLF1, TAB2, CDK12, SMAL1, SACS, MAT2B, MYOF, ITSN2, ARHGC, CNOT2, VSX1, CWC15, RAI14, H2AW, RM27, VPS54, CAMP3, PHRF1, DAPLE, ZFAT, RELCH, DIP2B, JCAD, SLAI2, BAHC1, PAK5, CHD7, F135A, RRBP1, MAP10, CE126, CPSF2, KLHL9, SYLC, C2D2A, DISP3, TBC14, RBM27, KANL3, HECW2, STAR9, RERE, ANKY1, IMPCT, HNF6, HSFX1, RBX2, MYOTI, PRGC1, ARP21, GULP1, SAE2, POLK, DBF4A, NXF1, ZMYM2, REV1, ZNF70, S14L4, DAXX, ADDG, HYPDH, FXL17, CCD39, ABCF2, S23A2, AAKG2, KDM5B, SYWM, TCF20, SUN2, NDOR1, AFF4, SEPT9, UBQL2, IP6K2, NUFP1, SMPX, S30BP, MED13, PFD2, NRBP, FEZ2, EVL, CTNA3, XPO7, BAZ2B, BAZ2A, BAZ1B, HERC5, SIX4, ZMYM5, HACL1, STAG3, HOOK1, NGAP, ZN391, SALL4, S2513, FBXL7, ZN112, DBNL, ZN229, ZN180, HSPB8, KS6A6, DBR1, FBXL4, FBXL2, GMEB2, PO2F3, GPTC8, C8AP2, FBX4, FBXW2, IKZF3, TRHDE, HDAC9, ACINU, AGO2, NUP50, ZHX1, DSE, SARDH, CFA45, AGO1, ZN236, ZN214, MKLN1, NRX1A, PADI1, ZN777, INTU, ZN608, WWC3, F184B, INO80, KDIS, MRTFB, ZBT21, NEB1, AT7L1, K1210, PKHG1, SHRM4, PKHH1, YETS2, CNOT6, HECD1, ZMYD8, HSF4, PADI4, APC10, MYO6, SPAT2, KMT2B, CAN11, PHTF1, MAGD2, CSN3, TTF2, BSN, MACF1, SCAF8, TRI33, PHF8, LIMC1, TRI35, TNR6B, PLCL2, EXOC7, SMAG1, CE164, CBPC1, SATB2, UN13A, DICER, SRRM2, PA2G4, CD11A, CTND2, BAIP2, SCML2, RUVB2, CDYL, HIG1A, AKT3, PRLD1, PLAP, T53G5, ADIP, ICE1, EFR3B, PKHA6, MAST1, AMOL2, ZBTB1, KDM2A, FRM4B, FAN1, KLH20, CRYL1, AXIN2, GUAD, MAN1, TR150, MED16, ZBT32, MTO1, SYYM, ZBT12, CAB39, LC7L2, RBMX2, HDGR3, BOLA1, STA13, T22D4, RL36, C2CD2, ZN175, DMXL1, TRRAP, MTCL1, ZN451, WDR7, C170B, RIPR2, TLN2, DTNA, CRBG1, LAS1L, AFG32, PRC2C, PPME1, TRI17, CEP83, PAXB1, SP16H, MAGD1, KLF2, SNX5, LRRF2, FHOD1, IRAK3, NCOR2, GMEB1, BIG2, MD1L1, RM42, ATP23, SNCAP, CABIN, OAS3, NEMO, SQOR, NCOA3, NUMBL, Z780B, CCD61, SCIN, PCLO, SETBP, MORC2, NS1BP
Species: Homo sapiens
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Kawauchi K, Araki K, Tobiume K, Tanaka N. Loss of p53 enhances catalytic activity of IKKbeta through O-linked beta-N-acetyl glucosamine modification. Proceedings of the National Academy of Sciences of the United States of America 2009 106(9) 19202066
Abstract:
The IkappaB kinase (IKK)-NF-kappaB pathway plays a critical role in oncogenesis. Recently, we have shown that p53 regulates glucose metabolism through the IKK-NF-kappaB pathway and that, in the absence of p53, the positive feedback loop between IKK-NF-kappaB and glycolysis has an integral role in oncogene-induced cell transformation. Here, we demonstrate that IKKbeta, a component of the IKK complex, was constitutively modified with O-linked beta-N-acetyl glucosamine (O-GlcNAc) in both p53-deficient mouse embryonic fibroblasts (MEFs) and transformed human fibroblasts. In p53-deficient cells, the O-GlcNAcylated IKKbeta and the activating phosphorylation of IKK were decreased by p65/NF-kappaB knockdown or glucose depletion. We also found that high glucose induced the O-GlcNAcylation of IKKbeta and sustained the TNFalpha-dependent IKKbeta activity. Moreover, the O-GlcNAcase inhibitor streptozotocin intensified O-GlcNAcylation and concomitant activating phosphorylation of IKKbeta. Mutational analysis revealed that O-GlcNAcylation of IKKbeta occurred at Ser 733 in the C-terminal domain, which was identified as an inactivating phosphorylation site, suggesting that IKKbeta O-GlcNAcylation regulates its catalytic activity. Taken together, we propose a novel mechanism for the enhancement of NF-kappaB activity by loss of p53, which evokes positive feedback regulation from enhanced glucose metabolism to IKK in oncogenesis.
O-GlcNAc proteins:
IKKB
Species: Homo sapiens
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