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Zhang N, Meng Y, Mao S, Ni H, Huang C, Shen L, Fu K, Lv L, Yu C, Meekrathok P, Kuang C, Chen F, Zhang Y, Yuan K. FBXO31-mediated ubiquitination of OGT maintains O-GlcNAcylation homeostasis to restrain endometrial malignancy. Nature communications 2025 16(1) 39894887
Abstract:
Protein O-GlcNAcylation is a post-translational modification coupled to cellular metabolic plasticity. Aberrant O-GlcNAcylation has been observed in many cancers including endometrial cancer (EC), a common malignancy in women. However, clinical characterization of dysregulated O-GlcNAcylation homeostasis in EC and interrogating its molecular mechanism remain incomplete. Here we report that O-GlcNAcylation level is positively correlated with EC histologic grade in a Chinese cohort containing 219 tumors, validated in The Cancer Genome Atlas dataset. Increasing O-GlcNAcylation in patient-derived endometrial epithelial organoids promotes proliferation and stem-like cell properties, whereas decreasing O-GlcNAcylation limits the growth of endometrial cancer organoids. CRISPR screen and biochemical characterization reveal that tumor suppressor F-box only protein 31 (FBXO31) regulates O-GlcNAcylation homeostasis in EC by ubiquitinating the O-GlcNAc transferase OGT. Downregulation of O-GlcNAcylation impedes EC tumor formation in mouse models. Collectively, our study highlights O-GlcNAcylation as a useful stratification marker and a therapeutic vulnerability for the advanced, poorly differentiated EC cases.
O-GlcNAc proteins:
FR1L5, ERIC2, PKHG3, CCD78, ZN320, WDR27, MBPHL, CFA69, CDHR4, PINLY, VWA3A, NPB15, AKD1B, CC154, AGAP5, MET15, SAC31, CB081, TTL13, ENO4, CFA96, ZSWM8, OCAT2, NPIB5, LYRM9, ZBBX, CMI2B, NOTO, ARG33, CMA1B, DCD2C, IQCF6, ZN487, SHSA9, ADM5, PROB1, PTG3L, TM262, CK098, CS084, DCDC1, BACH, S28A1, SYT5, VMA5A, PITM1, MPP10, CCL22, EST2, P3C2B, UBE2C, TOR1A, P5I11, RPC1, PSA7, TR13B, RGS12, HAT1, CE290, NPFF, PGRC2, NPHP1, SIVA, TRI18, HMGB3, MRP3, INSI1, SRGP3, ADCY6, FGF16, IF4G3, ADA20, HTSF1, RAD21, NPA1P, L37A3, EREP2, NMD3B, TSN1, DPM1, TOM1, NSMA, HUS1, CTNS, AOC2, NPHP4, SNN, PROP1, PEX14, MED24, Z324A, UBP2, ZMY10, SPI2, IDHC, RBBP9, SOAT2, SPF27, DNJC8, FGF18, UBP1, BAIP3, FARP2, ZN432, KDM4B, HEXI1, UPP2, REC8, NDUB4, MRP6, RASL1, TACC2, RPGF3, BAG4, ATS2, ACSL3, RAB36, FRITZ, DRC4, CCNE2, ANF, PROC, PDGFA, LCAT, B3A2, CFAI, CO5A2, PGK2, RU2B, FGF4, PKHD1, SPRC, INHBB, F163B, OST4, PRR35, PAL4G, CGB3, VSIG8, COX8A, MYBB, RALA, CD79A, PCNA, ECP, PPA5, PRG2, OXDA, ZNF44, RFA2, UD2B7, STMN1, YBOX3, ZNF19, ZNF23, INAR1, SAP3, PRS6A, GBRB1, TNR1A, AOC1, AMY2B, PSB1, LMNB1, CAN3, CP3A5, HNF1A, CP2A7, ENDOU, ZNF10, DRD4, CCNO, CP7A1, CRYGS, EST1, RIR1, PAR1, MCM3, PSA2, PSA3, HMGB2, KAD4, PSB6, MZF1, RBL1, PTPRM, 3MG, PBLD, STX2, ERD22, MCM5, GALNS, SDC2, BMP8B, SPB6, RFA3, DEK, PRS7, GGT2, TNR3, TALDO, IF4A3, FEN1, HNF4A, M3K8, LAP2A, LAP2B, STAT6, MTHR, AL3B1, S15A1, MSS4, RFX2, INAR2, PRC2A, HSP13, GCST, PAXI, MAPK2, RPIA, CENPA, CENPF, PRI1, ACADV, NUMB, 5NTC, GUAA, DNLI4, ZNF83, IRAK1, CCR8, CLCN7, VAV2, ZN140, BIEA, MK10, OAZ1, AT1B3, DRG2, RAD, FGF8, UCN1, FOXA1, ALR, CTBP2, BCAR1, WDR4, CORO7, FBXW4, CABP4, RAB15, DJB13, SC61G, PTEN, SRP54, CKS1, PFD3, SUMO2, PP1A, PRS4, RUXG, LSM3, TYB4, TRA2B, 3BP2, RBM6, RPP38, HEPC, GPSM2, BAT1, RT35, CBX1, METK1, TF2B, CDK3, E2F1, MLRA, MYL5, ID2, P, HGFA, LGUL, RAD51, MCL1, PDE4C, SG11B, F27E3, DMPK, R51A2, INCA1, CF210, MGAT2, SFSWA, BIRC1, PAFA, IFT88, KLF10, SEM3B, PHLP, PPIG, PEX6, RB33A, DPOA2, SRC8, FLOT2, GALE, SLBP, HABP2, MCM6, TTLL4, RRP5, 2A5D, CND2, SPCS2, AR6P1, K0040, PEA15, CDK10, PON2, 2A5A, IRF4, TAF5, TAF1C, TRBP2, TRIP6, ZNF79, E2F4, ZN239, SNAT, NFE2, STX1A, MEA1, MK06, CDKN3, THTR, PCKGM, ZN827, MOONR, CL16A, MTHSD, FA83E, CF184, TECT1, PRSR3, TXIP1, CCD57, HKDC1, FHOD3, BTBDG, GFOD2, TKFC, TTLL9, DRC12, CDNF, HYDIN, SRCRM, PCDP1, CCD40, IQCC, PLCH1, VAS1L, PDCD4, LRC23, ZC21C, T4S20, FBLN7, CC157, M3K19, PAN3, TRI61, HERC4, MDH1B, ZN311, CC038, DYLT4, MEIG1, RRP12, WDR38, EFHC1, COL12, PA2GC, MANEA, PKHS1, SNPC4, F201A, F120S, MORN1, CFA70, UBX11, AXDN1, MRP7, ZFY27, AGRF1, CFA58, KIF24, SYT6, IER5L, ARM12, KAD9, DAAF9, CF163, RHG40, TMCO4, STPG1, EFCB6, CROCC, MEX3C, CBPC2, MCAF2, GP157, AXA81, CCD30, AGAP6, SLX4I, NXNL2, ARMC3, TTC23, FBX31, FBXW9, AL2CL, KFA, ATG9B, FTM, SLN13, FRPD2, Z518A, DMKN, TTLL5, ABLM2, ELP2, IQCE, CCSAP, ACD10, LCN12, OGFD2, NANP8, SAPL1, PWP2B, SWAP1, EFC12, NXRD1, ANR54, RM14, LTMD1, WDR93, EDC4, CP046, WDR73, PRS54, CP087, HAGHL, DCR1A, ATAD2, SPG17, ATRAP, ZN474, PLPR3, NHS, CC171, MAP12, GLB1L, BI2L2, RBP10, NSMF, CSC2A, DNMBP, DJC14, THADA, ZN497, LRC69, TMM91, DG2L6, PKHG7, MMS22, RHG27, FA47E, TM1L2, TTL10, KCP, UBP43, SMIM5, MED25, ZN765, CENPQ, MCM10, STRAA, MICA3, ZN367, APTX, TMC4, MUC19, DPOLN, SAXO4, CEA19, ADAT2, CATIP, ZN605, MYPN, YRDC, NHRF4, NLRX1, CAPS2, ST32C, THOC4, SESD1, WDR5B, TMM17, DAA11, NUD13, CNDG2, CTSR3, TXND6, DZIP3, PTH, TDRP, MYLK4, CASC2, RN135, CF337, ZN584, FMNL3, MSTN1, T151B, TRI59, CD302, CMA1C, DRC2, PGKA1, DRC7, CKP2L, DI3L2, SUV3, CCD13, SYTL1, REM2, CC170, KATL2, CFA46, RN168, DZI1L, AGRF2, CDK20, ASPM, TENS4, CENPL, ATOH7, F177A, ORML3, AHI1, CF107, ARG28, PYRD2, ABD12, LRC43, OR2LD, BBS5, PHTF2, TXND3, SVOPL, MINK1, ARL14, SPA6L, CCD24, LRC71, ARRD1, CC022, CCD33, TM148, CN178, BEND7, ADGB, CL076, ENDOV, S2529, CB069, IGS22, MUT7, CI163, SR1IP, ANR53, DAAF3, NLS1, NETO2, ZN485, MACA2, ADAD2, MORN4, CFA43, ZN248, TT21A, NSUN7, CS018, TTC16, DEN6B, ARMC2, DAAF1, TRPV1, WDR19, ANKK1, BHE22, BBS1, CC148, BEST4, NLGNY, CADM4, NEK11, OR1K1, O13C5, SVIP, DNJB8, CLHC1, GA2L2, ZSC18, PMFBP, ADA32, MIEAP, FANK1, SPP2B, SACA4, DLG5, NSUN6, TBCK, ZDHC1, NEUFC, S38A5, BLNK, OSCP1, SNR27, SKA2, TFB1M, STAG1, CQ050, TEKT4, DYDC1, SPIR2, S13A3, MB3L1, SREK1, MT21A, ASB13, ATS14, DYH7, PPM1E, TM234, CV015, TCPW, GBF1, LAR4B, NPIB3, PXDN, RSLAA, N42L2, DNSL2, OSTF1, HPS1, CLP1, WNT8B, SCAM4, TF3C6, LSM10, PMEPA, AKTS1, LENG9, ELMO3, ARL8A, ZN669, TIFA, EAF2, RB39B, DYH11, DRC10, RRFM, NGBR, OMA1, ZN837, CHFR, ADAT3, NEIL1, KIF12, IFT43, LRC46, HMCES, MED8, FAH2A, MSD3, CCD34, ZN845, RSRC1, TXD15, MRP9, MRP8, CHAP1, LRIQ1, BT3L4, DNJC1, RPGR1, ALPK3, IFT74, CCD17, CC74B, LRGUK, CFA53, KAD8, STAC3, HEXI2, PPM1M, CFA57, NOL4L, F218A, SPT33, CFA54, ZN396, SPT13, ODAD4, PCFT, AGAP4, FCRL4, ERMAP, ALS2, PRAM, ALPK1, 1A1L1, FCRL5, S26A8, MED15, IF140, CEP89, MBOA4, MMS19, INSM2, TBX5, TEAD3, CDCA3, SPSB2, RAD9A, ZN184, MGLL, ATX2, BARD1, FOXB1, SPAG8, RNZ2, TCF25, MEP50, LBHD1, PSD2, NEUL2, PIGQ, CPPED, HDHD3, GCP2, FEM1A, PHAF1, FUZZY, CHCH7, DERL1, DHRS6, RSRP1, KTNB1, KIFC3, DPCD, SMIM2, IFT27, THIC, NADAP, TM2D2, BBS2, TEKT3, IDI2, NUSAP, CAYP2, STK33, TRI55, BCDO2, DB126, FRMD8, PITM2, OSBL7, ULBP1, CHIA, B2L14, TSG10, SPEF2, ZFHX2, CFA74, ZN436, DYH6, LRC27, BSSP4, DNAI2, CHST5, CLPB, DRC9, ENKD1, TKTL2, MMP28, MIXL1, ZN106, VCX1, ABHGB, TOR3A, FA83D, COE3, MROH8, CSTP1, TM231, TASP1, CS044, CJ095, TBA4B, WDR76, CN093, COG4, MLXIP, KIF9, S28A3, SIAE, CLSPN, CYBP, NMUR1, IF122, PARVG, SPC25, LST2, ARGAL, NCK5L, LRC4C, SPCS, NRX3B, EMC7, UBE2T, SLAF7, TMM9B, TF7L2, IFT46, XPP3, ANM8, AAAS, STK36, SOSSC, GLRX2, CLTR2, KIF15, SEM4G, CT096, MITOS, KLH11, HAUS2, MED9, CB042, SIR5, MKS1, P4HTM, ARH38, PP4R2, BTG4, APC11, WSB2, MYOF, C1RL, CC167, KCMF1, RN181, SPAT7, CAC1I, DYH1, KIF17, C2D2A, MYEF2, ANKY1, SAE1, IF172, DPOLL, NAT8, RPGFL, NDUAC, SCNBA, DNAI1, TEKT2, PS1C1, KAD3, APC5, GGA1, DJC12, FBXL2, NXT1, RALY, TSN16, FBX5, INTU, TPC1, ABT1, AKP8L, GUC1B, PCDGG, PCDA6, RHG26, RBL2B, B9D1, ANR26, CE164, MOK, SPG7, LAMP3, COLQ, DLEC1, PSF2, KCNK6, INVS, ASF1A, FBW1A, VP9D1, SL9A8, WDR37, GSTK1, RT28, RPC10, UB2J1, COQ4, EXOS1, CBY1, DYR1B, AAKB1, NRX3A, C170B, SPEF1, IFT25, SHAN1, ASB4, CEP83, PCDGM, TM14A, CABIN, USH1C, TNR11, SCIN
Species: Homo sapiens
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Li J, Li Z, Duan X, Qin K, Dang L, Sun S, Cai L, Hsieh-Wilson LC, Wu L, Yi W. An Isotope-Coded Photocleavable Probe for Quantitative Profiling of Protein O-GlcNAcylation. ACS chemical biology 2019 14(1) 30620550
Abstract:
O-linked N-acetylglucosamine ( O-GlcNAc) is a ubiquitous post-translational modification of proteins and is essential for cell function. Quantifying the dynamics of O-GlcNAcylation in a proteome-wide level is critical for uncovering cellular mechanisms and functional roles of O-GlcNAcylation in cells. Here, we develop an isotope-coded photocleavable probe for profiling protein O-GlcNAcylation dynamics using quantitative mass spectrometry-based proteomics. This probe enables selective tagging and isotopic labeling of O-GlcNAcylated proteins in one step from complex cellular mixtures. We demonstrate the application of the probe to quantitatively profile O-GlcNAcylation sites in 293T cells upon chemical induction of O-GlcNAc levels. We further applied the probe to quantitatively analyze the stoichiometry of O-GlcNAcylation between sorafenib-sensitive and sorafenib-resistant liver cancer cells, which lays the foundation for mechanistic investigation of O-GlcNAcylation in regulating cancer chemoresistance. Thus, this probe provides a powerful tool to profile O-GlcNAcylation dynamics in cells.
O-GlcNAc proteins:
A0A0B4J203, A0A0C4DFX4, SBNO1, P121B, CX028, RGPD3, AN36A, P121C, GG6L6, S31C2, E9PCH4, H0YAE9, H0YHG0, GG6LV, H3BMH7, PDLI1, TAF4, BCL9, ABLM1, CHD2, KMT2D, RGPD8, OPLA, HGS, MYPT1, ZN609, SC16A, SET1A, TIF1A, EIF3H, TET3, M3K7, PRPF3, TPD54, IF4G3, E41L2, AKAP8, TM11D, MYPT2, GANP, PLIN3, MAFK, BRD4, MITF, N4BP1, ATG13, PP6R2, ANR17, NCOR1, SPAG7, SRS10, SF3B1, CSDE1, TOX4, PCF11, AGFG2, SMC2, M3K6, SC24B, ZBT11, CNOT4, EYA4, OXSR1, ZMYM6, CCNE2, ANGT, LMNA, ALDOA, GCR, HSPB1, F13B, RLA2, K1C18, K2C8, ZFY, SRPRA, RU17, VIME, RU2A, ATX1L, RGPD1, S31C1, GLI3, LYAG, PABP1, COBA1, CO6A3, MYH7, ENPL, ZEP1, RS2, ZFX, ZNF30, ANPRC, ATF7, EGR1, SON, RCC1, ATF1, ATF6A, HXA5, ROA2, CBL, IF4B, GATA2, RIR1, RAE1, APC, ATPA, ARNT, MAP4, HXD9, HLAF, CLIP1, ZEP2, MYH10, TIE1, NU214, DEK, PDE6B, SRP14, CUX1, LPPRC, GATA4, KI67, YAP1, RFX5, SOX2, PRC2A, NASP, CDK8, NU153, RBP2, TAF6, EMD, PAPOA, NEK4, AGFG1, NUP98, INHBC, CADH6, F193A, KGD4, RT34, SARNP, LACTB, COG7, FOXK1, DAB2, PLIN5, SPTB2, SP2, NRG1, IF4G1, K1C17, TLE1, TLE4, UBE3A, ACK1, AHNK, FCHO2, FOXO1, TROAP, BPTF, IRAG2, BFSP1, FOXC1, PRDM2, DDX10, G3BP1, PABP4, GRB10, PPIG, MADCA, PICAL, MAMD1, CUL4B, ASPP2, SPTN1, CDK13, CYLC2, DSG2, UBP2L, SRC8, ITPR3, PUM1, MDC1, EPN4, RRP1B, NCOA6, RRP5, RFTN1, R3HD1, WDR43, EEA1, MTFR1, SF3B3, RYR3, SF01, JHD2C, ELF2, MYLK, TAB1, ZYX, ADRM1, QSER1, CL16A, RHG31, AAK1, TMM44, AMOT, IF44L, YIF1B, AG10A, CD048, FSIP2, ESCO1, S2553, BCORL, AN36C, MTUS2, PRC2B, CEP78, SAMD9, TSBP1, LRIF1, CXG2, SKT, ZN648, UBAP2, RBM26, RC3H1, EFCB6, CE350, RPRD2, S31A6, TASO2, ECM29, RN123, PLCX3, ARID2, DEN2C, K0930, LIN54, M18BP, SCYL2, NFRKB, KLH35, ZC3HE, ANR11, FIP1, SBSN, S49A3, FAT4, MCAF1, BCOR, DUSTY, GGYF2, BNC2, CO039, SRCAP, UBN2, FOXNB, UBP54, HAKAI, ASXL2, KNDC1, SPT6H, TAOK1, KDM3B, RGPD4, POGZ, NUFP2, EMSY, I2BP2, SH3R1, HUWE1, YTHD3, FLIP1, KAISO, MYPN, TTC6, LDB1, TM135, TBC26, ZFHX4, ANGL5, SPAS2, DZIP1, P66A, AHNK2, FMNL3, NAV2, ARI3B, MGAP, RP1L1, CC28A, Z3H7A, CDAN1, ANKH1, SUGP1, PHAR4, KMT2E, XRN1, SPART, NUP93, ZN687, CMTR1, THMS1, AN36B, TMTC2, SYNPO, FNBP4, GG6L1, ENAH, GG6L2, SLAI1, PHC3, BD1L1, NUP35, DDX55, NEIL3, GSDMB, ALMS1, STK35, GEMI5, RPGF6, SMCR8, WIPF2, TM171, RN133, TEKT4, LMO7, CKAP2, ATX2L, ACO11, P66B, DAAF4, BBX, FIG4, ZN516, RREB1, FUBP2, LPP, E2F7, TTC28, TOM6, ASTRA, OTUB2, PGBD4, LEG12, ELP4, RBM33, MYEOV, SMRD1, DDX27, P121A, TONSL, PDLI5, THOC3, VCIP1, LRIQ1, ZFR, EP400, CBPC4, RBM14, IPP2L, QKI, PLIN4, JMJD8, RBM15, MINT, SEC62, AGAP2, RGPD5, ATX2, MYD88, ARI3A, SPI2A, SPI2B, DPH2, MCMBP, TMPSD, YTHD1, WNK3, PP12C, TB182, TANC1, CEP44, SENP6, BRD8, RGAP1, ALX4, KI13A, KCNH6, ZN106, FOXP1, PABP3, SMOC2, WNK1, ZHX3, CP095, REEP4, DOCK5, ZN703, GORS2, MLXIP, PKHA5, FOH1B, RC3H2, TANC2, TRPM3, SYTL2, CP4FC, GAK5, JPH1, APMAP, DMAP1, GP108, KMT5A, GPR84, DUOX2, DUOX1, PCDBG, MDN1, NALP2, CARF, HXC10, TAB2, CDK12, ADA2, ITSN2, F135A, SI1L2, RBM27, KANL3, ZN219, DYH17, AFF4, NB5R1, S30BP, NRBP, BAZ2A, SIX4, HOOK1, TASOR, GMEB2, ZHX1, TAOK2, CFA92, MRTFB, ZBT21, PRR12, YETS2, HECD1, MYO6, ICAM5, MAGD2, SCAF8, TRAK1, SHAN2, SRRM2, EXO1, SCML2, POK19, POLH, NCKP1, AT11B, NOP58, ZN281, UB2J1, GRIP1, SALL2, ARIP4, RPGF2, HYOU1, TTLL3, PRC2C, PCDB4, NCOR2, CP46A, 5MP1, CABIN, NCOA3, S23IP, U3KPZ7
Species: Homo sapiens
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