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Xu S, Yin K, Xu X, Fu L, Wu R. O-GlcNAcylation reduces proteome solubility and regulates the formation of biomolecular condensates in human cells. Nature communications 2025 16(1) 40307207
Abstract:
O-GlcNAcylation plays critical roles in the regulation of protein functions and cellular activities, including protein interactions with other macromolecules. While the formation of biomolecular condensates (or biocondensates) regulated by O-GlcNAcylation in a few individual proteins has been reported, systematic investigation of O-GlcNAcylation on the regulation of biocondensate formation remains to be explored. Here we systematically study the roles of O-GlcNAcylation in regulating protein solubility and its impacts on RNA-protein condensates using mass spectrometry-based chemoproteomics. Unexpectedly, we observe a system-wide decrease in the solubility of proteins modified by O-GlcNAcylation, with glycoproteins involved in focal adhesion and actin binding exhibiting the most significant decrease. Furthermore, O-GlcNAcylation sites located in disordered regions and with fewer acidic and aromatic residues nearby are related to a greater drop in protein solubility. Additionally, we discover that a specific group of O-GlcNAcylation events promotes the dissociation of RNA-protein condensates under heat stress, while some enhance the formation of RNA-protein condensates during the recovery phase. Using site mutagenesis, inhibition of O-GlcNAc transferase, and fluorescence microscopy, we validate that O-GlcNAcylation regulates the formation of biocondensates for YTHDF3 and NUFIP2. This work advances our understanding of the functions of protein O-GlcNAcylation and its roles in the formation of biomolecular condensates.
O-GlcNAc proteins:
MEX3A, CNOT1, RGPD3, P121C, MYO1G, H7C0N4, PDLI1, CBX4, TAF4, RFXAP, PODXL, ARI1A, UTY, ABLM1, DVL1, KMT2D, HGS, MYPT1, XPO1, SET1A, PUR4, FYB1, PPM1G, EIF3H, IPO8, NUP42, KDM6A, ZZEF1, TET3, SI1L1, CP110, SYNJ1, IF4G3, TGON2, WIPF1, HTSF1, MYPT2, SMCA5, GANP, MA1A2, DIAP1, PLIN3, MAFK, KIN17, CUTA, N4BP1, CLAP2, BRE1B, PP6R2, ANR17, ZN217, FLNB, NCOR1, SPAG7, TACC1, GGYF1, ERLN1, WBP4, U520, WDHD1, RNH2A, STAM2, CBPD, STK10, TOX4, ST65G, TOX, PCF11, ENDD1, UBR5, AGFG2, KIF4A, MPZL1, IPO7, BAG4, SC24B, HERC2, ZMYM6, BAG3, CLPT1, ABL1, ADA, LDLR, HLAB, TFR1, CATA, GCR, KITH, HLAA, RPN2, ITB2, RLA2, RLA0, ITB1, RB, TPM3, SAP, LAMB1, SP1, PTPRC, ITA5, VIME, SNRPA, ROA1, ATX1L, DERPC, MYBA, CH60, PABP1, TPR, SKI, XRCC6, LAMP2, ITA4, HCLS1, KPYM, PO2F1, RAC2, IGLL1, RS2, TFE2, LEUK, CREB1, GCFC2, ATF7, SON, ATF1, TFE3, NFKB1, AL5AP, PUR2, ROA2, CBL, IF4B, AT2B4, APC, MGAT1, ARNT, DCK, PYR1, CALR, MAP4, CALX, NDUS1, PML, PDIA3, HMOX2, AMRP, CLIP1, ZEP2, HNRH1, ELF1, ICAM3, TTK, CAH8, BMI1, PTN7, RFC1, ADDA, NU214, MP2K2, HPCL1, VATA, CUX1, TXLNA, MLH1, PEX19, S19A1, LAP2A, LAP2B, STAT1, EPS15, MATR3, KI67, CRKL, UTRN, CAPZB, RFX5, PRC2A, NASP, FAS, CDK8, YLPM1, NU153, RBP2, TAF6, EMD, TCPQ, PAPOA, PLCD1, HCFC1, AFF3, ROA3, AGFG1, RBM5, ACLY, SMTN, RD23A, AF10, DSRAD, CADH4, SEC13, IF6, STX17, CORO7, NU107, SELB, TPIS, RAB2A, DCAF7, TIM10, CNBP, TBA1B, NOMO3, F193A, IGBP1, IF4G2, GTF2I, PHC1, NUCB2, TMF1, RT09, SARNP, FOXK1, FBLN2, FAM3A, RBM10, CDK6, HNRPU, SPTB2, FOXK2, RUNX1, CAP1, MEF2A, SP2, KMT2A, IF4G1, TLE1, TLE2, TLE3, TLE4, REL, GFPT1, GABPA, RING1, VAC14, EP300, AHNK, BRME1, MGAT2, GALT2, TROAP, TROP, BPTF, SFSWA, DPYD, TP53B, IRAG2, NFAC3, ROA0, AIMP2, GPS2, PABP4, S39A6, PICAL, HDAC1, STIM1, MTMR2, CUL4B, ASPP2, PEBB, NFYC, LRP8, VEZF1, BOP1, SEPT6, UBP2L, MLEC, ZMYM3, SRC8, LAGE3, PUM1, EPN4, RRP1B, NCOA6, GSE1, MEF2D, NFIX, ZN638, NUMA1, CND2, CND1, RB3GP, NECT1, PCBP1, PCBP2, ELOC, KS6A1, SC23B, JHD2C, ELF2, TAB1, NCOA1, ZYX, ADRM1, DPYL2, TAF9, DREB, DGUOK, QSER1, RHG31, AAK1, QRIC1, LRRF1, GNPTA, C2CD3, EPC2, PDCD4, BOREA, PAN3, BRD10, TGO1, PRC2B, PCID2, P4R3B, DCA10, SNP47, MANEA, ZN362, LRIF1, CAF17, CAMP1, UBAP2, CPTP, RC3H1, AHDC1, VPS53, RPRD2, ZN318, TASO2, ZMYM4, PAPD7, RN123, MAP1S, ARID2, NIPBL, LIN54, ANR54, PPR18, EDC4, SCYL2, GOLM2, NFRKB, RSBNL, MDEAS, BRAT1, ZC3HE, LARP1, FIP1, CRTC3, SHSA2, PI16, MCAF1, BCOR, GGYF2, NFXL1, QSOX2, YJ005, UBN2, MTSS2, NOL8, SSH2, ASXL2, SPT6H, LRC8D, EIF3M, MEPCE, KDM3B, TRM1L, ZCCHV, EFL1, KANL1, POGZ, ZFY16, NUFP2, MAVS, EMSY, I2BP2, HUWE1, YTHD3, KAISO, LDB1, LYRIC, RETR3, TSYL5, DZIP3, CACL1, P66A, C2CD5, HIPK1, ERI1, DEN1C, VRK3, ARI3B, MGAP, Z3H7A, CDAN1, ANKH1, SUGP1, GLT12, K2013, PHAR4, DCP1B, XRN1, RPTOR, NUP93, ZN687, FNBP4, NOPC1, ZBTB2, EMC1, CB069, EIF1A, KRI1, AFG2A, NHLC2, AVL9, XXLT1, GOLM1, SUMF2, TXND5, KCT2, CHSTE, SLAI1, TNR6A, PHC3, SP20H, KMT2C, BD1L1, ARI1B, NUP35, KNL1, MSPD2, NEDD1, GABP2, PIGX, STT3B, ALMS1, NEK9, NEK7, PO210, GEMI5, PIGO, MZB1, RAB2B, TM263, NUDT8, ZFN2B, HNRLL, PCNP, LMO7, ATX2L, P66B, GBF1, SMG7, RTF1, TOPB1, TSC1, PRCC, RREB1, CBP, DDX17, SEM4D, GSLG1, RENT1, GPKOW, FUBP2, ARHG2, UBP7, LPP, IGSF8, MRTFA, ACD, RAB37, PF21A, DOC10, DCPS, FAF2, TMCO6, ESS2, RMI2, TONSL, PDLI5, ZN414, VCIP1, PDLI2, ANCHR, ZFR, EP400, PRRC1, RBM14, QKI, PURB, SPAG5, CIC, MED15, ERGI2, ERBIN, LYSM1, MYADM, SEBP2, RUFY1, MINT, HTF4, CNN2, AGAP2, CSN8, CGRE1, DOK1, CTIP, SMAD5, S29A1, ARI3A, ANM1, DPH2, PELO, ERP44, ESYT1, CNPY3, WAC, MMTA2, HNRL1, ALG8, TMUB1, YJU2, PAPOG, SSBP3, JAM3, OSB11, NAA15, EIF2A, MK67I, YTHD1, KPCD2, UCK2, FTO, AMRA1, CEP44, BC11B, YIPF3, BRD8, XYLT2, I2BPL, MEGF9, EPC1, SLK, ADNP, ZN106, TM245, TMX1, CENPH, WNK1, ZHX3, DOCK5, PKHG2, KANL2, PKHA5, CLSPN, MYG1, RC3H2, LY9, TAF9B, S38AA, TM165, NCOA5, TANC2, TNR6C, CHD8, RESF1, APMAP, ARFG3, UBN1, GP108, INCE, ANLN, GEPH, BMP2K, RBM12, STAU2, INT10, GPT2L, CARF, PP4R2, TAB2, RM39, EURL, CDK12, HPBP1, ITSN2, ARHGC, CHMP5, FOXJ2, SLAI2, CT2NL, TBC14, RBM27, KANL3, FRM4A, ANFY1, GMPR2, ZN219, SE1L1, B4GT7, STK39, SEC63, SUN2, SRP68, SEPT9, UBQL2, S30BP, PFD2, NRBP, EI2BD, BTNL2, CDC23, GGA2, GMEB2, DP13A, MA1B1, ACINU, NUP50, MRTFB, ZBT21, YETS2, HECD1, TPX2, MGT4A, SYNRG, MINP1, SCAF8, SET1B, TBD2B, DICER, SRRM2, SMC3, SCML2, ZN148, CLC11, POLH, PLAP, TPPC8, WBP11, GIT1, ZN281, SIT1, HBS1L, SALL2, TRRAP, ARIP4, HECD4, CRBG1, HYOU1, ATG4B, KLF12, PRC2C, RBM7, CD2AP, SRPRB, GMEB1, TACC3, STK24, NCOA3, M3K4, ZHX2, NS1BP
Species: Homo sapiens
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Hou C, Deng J, Wu C, Zhang J, Byers S, Moremen KW, Pei H, Ma J. Ultradeep O-GlcNAc proteomics reveals widespread O-GlcNAcylation on tyrosine residues of proteins. Proceedings of the National Academy of Sciences of the United States of America 2024 121(47) 39531497
Abstract:
As a unique type of glycosylation, O-linked β-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) on Ser/Thr residues of proteins was discovered 40 y ago. O-GlcNAcylation is catalyzed by two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), which add and remove O-GlcNAc, respectively. O-GlcNAcylation is an essential glycosylation that regulates the functions of many proteins in virtually all cellular processes. However, deep and site-specific characterization of O-GlcNAcylated proteins remains a challenge. We developed an ultradeep O-GlcNAc proteomics workflow by integrating digestion with multiple proteases, two mass spectrometric approaches (i.e., electron-transfer/higher-energy collision dissociation [EThcD] and HCD product-dependent electron-transfer/higher-energy collision dissociation [HCD-pd-EThcD]), and two data analysis tools (i.e., MaxQuant and Proteome Discoverer). The performance of this strategy was benchmarked by the analysis of whole lysates from PANC-1 (a pancreatic cancer cell line). In total, 2,831 O-GlcNAc sites were unambiguously identified, representing the largest O-GlcNAc dataset of an individual study reported so far. Unexpectedly, in addition to confirming known sites and identifying many other sites of Ser/Thr modification, O-GlcNAcylation was found on 121 tyrosine (Tyr) residues of 93 proteins. In vitro enzymatic assays showed that OGT catalyzes the transfer of O-GlcNAc onto Tyr residues of peptides and OGA catalyzes its removal. Taken together, our work reveals widespread O-GlcNAcylation on Tyr residues of proteins and that Tyr O-GlcNAcylation is mediated by OGT and OGA. As another form of glycosylation, Tyr O-GlcNAcylation is likely to have important regulatory roles.
O-GlcNAc proteins:
NPIA9, RBM47, E2F8, SBNO1, CNOT1, P121B, HMX3, RHG32, P121C, NACAM, PDLI1, TAF4, DNM1L, PLOD2, CAC1A, ARI1A, CDKA1, NCAN, ABLM1, KMT2D, HGS, MYPT1, ZN609, SC16A, SET1A, TRNK1, OGT1, TNC18, P4HA2, NUP42, KDM6A, ASAP2, SI1L1, RFOX2, PRPF3, SYNJ1, IF4G3, MTG8R, E41L2, PLRG1, ZN207, BUB1, MYPT2, KPRB, ZN292, SI1L3, GANP, TBC12, OGA, KLH41, PLIN3, MAFK, ABCC9, TBL1X, MITF, SRGP2, SLIT3, T22D2, PP6R2, ANR17, LIPA4, ZN217, NCOR1, U520, RASF9, DYSF, TOX4, SC24D, FCSD2, PCF11, NFAT5, SC31A, AGFG2, SCAF4, ELP1, MRP6, SVIL, SC24A, SC24B, CNOT4, ZMYM6, BAG3, LATS1, LMNA, CATA, GCR, CPNS1, HSPB1, RPN1, RLA2, ITB1, K1C18, K2C8, NPM, CATD, GP1BA, SAP, CATB, SP1, PTPRC, NFIC, VIME, K1C19, SNRPA, ATX1L, LAMC1, ARY2, SRF, PABP1, TPR, SKIL, ENPL, PO2F1, B4GT1, ATF2, FOSL1, FOSL2, GNS, ZEP1, RS2, TFE2, CREB1, HXB6, ATF7, EGR1, SON, ATF1, NUCL, ICAL, OSBP1, RFX1, CBL, NFYA, IF4B, GATA2, ARNT, MAP4, GRN, CDC27, CLIP1, HXC9, ZEP2, ELF1, NU214, NUP62, CUX1, STAT3, BUD31, HNF4A, LAP2A, MTOR, PCP, MATR3, GATA4, UTRN, STT3A, RFX5, SOX9, PRC2A, NEST, HSP13, NASP, CDK8, YLPM1, NU153, RBP2, TAF6, EMD, PPT1, PAPOA, FXR2, KCNQ1, MYOM1, AGFG1, HNRPF, NUP98, SMTN, SC24C, ATX1, RD23B, AF17, DSRAD, MAZ, CTBP2, CSK21, F193A, SERB, IF4G2, GTF2I, PHC1, NGAL, KGD4, SARNP, FOXK1, DAB2, PGBM, RHG04, SPTB2, FOXK2, OTUD4, EWS, SP2, NRG1, SP4, SP3, PAX2, KMT2A, IF4G1, NOTC2, PTN12, GABPA, GABP1, CKAP4, ZO1, ACK1, TLE5, EP300, AHNK, ASPH, TROAP, BPTF, NFIA, TP53B, FOXC1, TAF10, PICAL, MAMD1, SQSTM, RIPK1, STIM1, CUL4B, NFYC, CDK13, CKAP5, VEZF1, UBP2L, GIT2, SRC8, CAPR1, PUM1, MDC1, EPN4, TTLL4, RRP1B, NCOA6, GSE1, MEF2D, ZN638, NUMA1, HECAM, R3HD1, DAZP2, KIF14, PDK3, EBP, NONO, LRC41, RBMS2, SSXT, NCOA2, SF01, MED1, JHD2C, T22D1, ELF2, TAB1, NCOA1, TBCC, ZFHX3, ZYX, CCDC6, TAF9, DREB, NRF1, GEN, RFX7, QSER1, AAK1, PRSR3, RGPA2, QRIC1, TB10B, TPRN, FIL1L, CRTC2, IF44L, YIF1B, NOM1, BCORL, DDX6L, BRD10, SH319, TGO1, PRC2B, CE170, ZN362, DCST2, ZEP3, ZC3HD, CSCL2, LRIF1, RHG21, UBAP2, RBM26, CF163, AHDC1, RPRD2, ZN318, TASO2, ZMYM4, PAPD7, TENS2, KANK2, ICE2, ARID2, TENS3, USF3, ANR40, BICRL, SDE2, NIPBL, LIN54, TET2, ZNT6, EDC4, SCYL2, TTC27, NFRKB, RSBNL, TT23L, NCEH1, MDEAS, ZC3HE, FIP1, CRTC3, SAS6, ARSK, MCAF1, BCOR, GGYF2, AEBP2, BNC2, NFXL1, CO039, SRCAP, UBN2, TM1L2, RAPH1, HAKAI, ASXL2, SPT6H, BOP, KDM3B, ZCCHV, NUP54, RGPD4, POGZ, ZFY16, NUFP2, MAVS, EMSY, RAI1, I2BP2, SDK1, SRGP1, RBBP6, SH3R1, YTHD3, CENPV, KAISO, MYPN, LDB1, LYRIC, ABCAC, BCL9L, CASZ1, TSYL5, CARM1, PRSR1, DDX42, CACL1, P66A, HIPK1, RB6I2, AHNK2, NAV2, GID4, ARI3B, TEX2, MGAP, Z3H7A, ANKH1, SUGP1, CCAR1, MILK2, GAR4, TBC21, PHAR4, XRN1, MAML2, SPART, NUP93, DOCK4, SYNPO, FNBP4, AF1L2, TAB3, NOPC1, IGSF1, ARFG1, ENAH, TM102, WDR31, MISSL, TNR6A, PHC3, SP20H, NAV1, VP37A, KMT2C, ARI1B, NUP35, KNL1, O52H1, PLBL2, NEDD1, SMRC2, TBC15, ZN507, ALMS1, DLG5, FNIP1, ZN384, WIPF2, PYRD1, D42E1, PCNP, LMO7, ATX2L, P66B, BBX, ELYS, ZCH14, PIEZ1, GBF1, RTF1, PHF3, MAML1, ZN592, LAR4B, SORL, TFG, TAF4B, RREB1, CBP, DDX17, GPKOW, M4K1, FUBP2, LPP, WNT2B, P33MX, ACD, FKB10, TTC28, PF21A, ZN669, ZN501, REPS1, RBM33, CERS2, GWL, P121A, CC120, PDLI5, SENP5, VCIP1, ZN462, CHAP1, LCOR, Z512B, ZFR, EP400, BMF, PRRC1, NOL4L, RBM14, QKI, PHF12, CIC, MED15, ERBIN, SIN3A, MINT, HTF4, EYA3, DNJC2, ELF4, RGPD5, ATX2, TS101, ARI3A, TEP1, DPH2, GPTC1, WAC, DIDO1, HNRL1, CP250, NUP58, RBM4, UBP26, YTHD1, BCDO2, B2L14, AMRA1, CE295, TANC1, ZC12C, CEP44, SP130, BRD8, I2BPL, RBNS5, EPC1, ADNP, HIPK2, ZN106, PTN23, WNK1, ZHX3, ZN644, HAUS4, SLAP2, YTDC2, PEAK1, PKHG2, ECT2, GORS2, MLXIP, PKHA5, CLSPN, CDHR5, RC3H2, TAF9B, NCOA5, TANC2, ZN532, TNR6C, CHD8, APMAP, UBE2T, DMAP1, UBN1, DCP1A, RTN4, PRD10, PDLI7, EI2BG, MBNL1, RNC, RBM12, INT7, CARF, ABI2, HXC10, TAB2, CDK12, GRHL1, ITSN2, BICRA, CNOT2, FLRT1, KCMF1, DAPLE, CHD7, F135A, RBM27, KANL3, RERE, LIMD1, TCF20, SUN2, UBQL2, TRPS1, S30BP, PUF60, NRBP, BAZ2B, SIX4, HOOK1, GGA2, TASOR, AKA11, GMEB2, PARP4, MYO15, MYH13, NUP50, ZHX1, CDV3, MRTFB, ZBT21, PLXB3, PRR12, YETS2, HECD1, ZMYD8, SPAT2, PRP19, SOX13, SCAF8, TRI33, TNR6B, SET1B, SATB2, SHAN2, HPS5, SRRM2, SCML2, R3HD2, ZN281, KLK5, ARIP4, MTCL1, RPGF2, CRBG1, HYOU1, PRC2C, RBM7, YTHD2, HCFC2, NCOR2, GMEB1, NCOA3, S23IP
Species: Homo sapiens
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Liu J, Hao Y, Wang C, Jin Y, Yang Y, Gu J, Chen X. An Optimized Isotopic Photocleavable Tagging Strategy for Site-Specific and Quantitative Profiling of Protein O-GlcNAcylation in Colorectal Cancer Metastasis. ACS chemical biology 2022 17(3) 35254053
Abstract:
O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation is a ubiquitous protein post-translational modification of the emerging importance in metazoans. Of the thousands of O-GlcNAcylated proteins identified, many carry multiple modification sites with varied stoichiometry. To better match the scale of O-GlcNAc sites and their dynamic nature, we herein report an optimized strategy, termed isotopic photocleavable tagging for O-GlcNAc profiling (isoPTOP), which enables quantitative and site-specific profiling of O-GlcNAcylation with excellent specificity and sensitivity. In HeLa cells, ∼1500 O-GlcNAcylation sites were identified with the optimized procedures, which led to quantification of ∼1000 O-GlcNAcylation sites with isoPTOP. Furthermore, we apply isoPTOP to probe the O-GlcNAcylation dynamics in a pair of colorectal cancer (CRC) cell lines, SW480 and SW620 cells, which represent primary carcinoma and metastatic cells, representatively. The stoichiometric differences of 625 O-GlcNAcylation sites are quantified. Of these quantified sites, many occur on important regulators involved in tumor progression and metastasis. Our results provide a valuable database for understanding the functional role of O-GlcNAc in CRC. IsoPTOP should be applicable for investigating O-GlcNAcylation dynamics in various pathophysiological processes.
O-GlcNAc proteins:
A0A0B4J203, A0A0C4DFX4, RBM47, E2F8, WDR27, SBNO1, CNOT1, P121B, P121C, H0YAE9, H0YHG0, H7C469, K7ELQ4, M0QZ24, PDLI1, HAX1, TAF4, BCL9, CAC1A, DDX3X, NFIB, PPP6, MA2B1, ARI1A, SOCS7, ABLM1, KMT2D, GBRD, RGRF2, TX1B3, HGS, MYPT1, SYN3, ZN609, TRI66, PDZD2, MAST4, SC16A, SET1A, CASC3, FOXP2, MOT4, P4HA2, ARPC5, CLOCK, MAFG, PER1, KDM6A, TET3, SI1L1, TGFI1, M3K7, MCA3, PRPF3, TPD54, SYNJ1, IF4G3, E41L2, WIPF1, FOXO3, TGM5, RNF13, SPY2, PLRG1, ZN207, AKAP8, CALU, ORC5, MYPT2, GANP, OGA, CCNT1, BUB1B, PLOD3, PLIN3, MOT2, MAFK, PQBP1, BRD4, TBL1X, PP1RB, NBN, MITF, SRGP2, N4BP1, ROCK2, PP6R2, CNOT3, ANR17, FLNB, NCOR1, SF3B1, REM1, CREG1, CRTAP, SYUG, CYTF, TOX4, TOX, SUN1, PCF11, AGFG2, UBE4B, CAC1H, SVIL, SC24A, SC24B, CNOT4, EYA4, ZMYM6, BAG3, LATS1, DDAH2, TXD12, ONEC2, CLPT1, ABL1, CRYAB, LMNA, TFR1, CATA, GBA1, FUCO, ALDOA, GCR, G3P, CPNS1, HSPB1, RLA2, RLA0, ITB1, K1C18, NPM, CATL1, CATB, MCR, BGLR, ITA5, NFIC, VIME, SNRPA, FGR, ATX1L, DERPC, ZN865, GLI2, MYBB, CLUS, PPAL, MPRI, PABP1, TPR, BMP3, SKIL, ENPL, PO2F1, PLAK, ATF2, ZEP1, RS2, TFE2, F261, ITB4, ZNF23, ZNF25, JUNB, ATF7, TPH1, DDX5, EGR1, SON, NELFE, ATF1, ATF6A, CADH2, ICAL, CSRP1, FLNA, RFX1, CBL, SFPQ, COF1, IF4B, GATA2, APC, DDX6, ARNT, MAP4, LYOX, HXD9, MZF1, CLIP1, 5HT1F, HXA11, ZEP2, ELF1, CTNB1, FBN1, ADDA, BASI, NU214, VGFR2, SRP14, NUP62, SYUA, VATA, CUX1, TXLNA, STAT3, LAP2A, EPS15, HELZ, MATR3, SSRA, SSRB, KI67, ATRX, MAP1B, YAP1, UTRN, STT3A, SC6A8, RFX5, SOX2, PRC2A, HSP13, NR2C2, NASP, CDK8, DHE4, YLPM1, NU153, RBP2, TAF6, MRE11, EMD, MXI1, MAP2, TOB1, PPT1, TCPQ, PAPOA, GDS1, AGFG1, CRIP2, NUP98, SMTN, SC24C, HIRA, ATX1, ATN1, AFAD, AF10, AF17, DSRAD, SEC13, NU107, ZN445, CSN2, RL37, WDR5, TIM10, F193A, RBM6, PITX1, IF4G2, PHC1, ADA17, KGD4, RL19, FOXK1, DAB2, RHG04, RBM10, HNRPU, SPTB2, FOXK2, RUNX1, MEF2A, SP2, SP3, PLOD1, KMT2A, TF65, IF4G1, NOTC2, TLE4, PTN12, CALD1, MEF2C, P5F1B, GABPA, ZO1, ACK1, EP300, AHNK, FCHO2, HMGX3, SRBP2, FOXO1, ASPH, TROAP, BPTF, FSTL1, NFIA, DPYD, TP53B, FOXC1, ECH1, ROA0, DDX10, TBX2, GPS2, G3BP1, PABP4, ADAM9, PICAL, NAB1, SERC3, RIPK1, IQGA2, STIM1, CUL4B, ASPP2, CAC1S, RUNX2, NFYC, CDK13, TOB2, VEZF1, UBP2L, GIT2, SRC8, CAPR1, LAGE3, PUM1, MDC1, EPN4, TTLL4, RRP1B, NCOA6, GSE1, MEF2D, LASP1, MYPC3, ZN638, NUMA1, SART3, CND1, R3HD1, KIF14, WDR43, PLCL1, PLEC, NOMO1, NONO, RCN1, RYR3, KS6A1, RBMS2, TAF1C, SF01, MED1, JHD2C, TRIP6, T22D1, ELF2, TAB1, HERC1, NCOA1, VAS1, ZFHX3, ZYX, ADRM1, SYPL1, TAF9, DREB, DGKD, CGT, GEN, LY6K, RFX7, QSER1, AAK1, PRSR3, QRIC1, MA7D1, WDR72, TBRG1, TB10B, TPRN, FIL1L, SVEP1, AMOT, EPC2, CRTC2, PAN3, HS904, YIF1B, AG10A, IGS11, ZN628, BCORL, FIGN, BRD10, SH319, TGO1, PRC2B, TOIP1, CEP78, P4R3B, HP1B3, CE170, ZN362, FKB15, AKND1, ZEP3, LRIF1, SWT1, RHG21, UBAP2, RBM26, DEP1A, OGRL1, AHDC1, F222A, RPRD2, RN220, ZN318, TASO2, ZMYM4, PAPD7, TENS2, KANK2, ARID2, USF3, RHG17, CYTSA, ANR40, BICRL, JADE1, PKHA7, NIPBL, LIN54, TET2, RINT1, CRCDL, ZNT6, TTC41, RHGBA, NFRKB, RSBNL, KCD18, NCEH1, MDEAS, ZC3HE, LARP1, NHS, CRTC3, SAS6, MCAF1, BCOR, MPRIP, DNMBP, GGYF2, THADA, BNC2, NFXL1, NBEL2, CO039, SRCAP, CBAR2, UBN2, XIRP1, RAPH1, LARP4, HAKAI, ASXL2, SPT6H, KDM3B, ZCCHV, KANL1, RGPD4, POGZ, ZFY16, NUFP2, MAVS, CLAP1, EMSY, I2BP2, SRGP1, RBBP6, SH3R1, HUWE1, YTHD3, NPM2, ILDR1, KAISO, MYPN, LDB1, LYRIC, BCL9L, LUZP1, NRAP, RTTN, PRSR1, DDX42, CEP57, CD20B, CACL1, P66A, HIPK1, KCC1D, RN135, MY18B, AHNK2, FOXP4, NAV3, NAV2, MISP, ARI3B, IPRI, TEX2, MGAP, CC28A, Z3H7A, ANKH1, SUGP1, RPAP2, MILK2, SRRM1, ZZZ3, GAR4, PHAR4, RTKN2, DCP1B, XRN1, PELP1, CKLF8, TENS4, SPART, RPTOR, NUP93, ZN687, DOCK4, RHG24, RUSC2, SYNPO, FNBP4, D2HDH, RP25L, ATPF2, CPSF7, ARFG1, ENAH, SPOT1, SUMF1, KCNH5, SLAI1, TNR6A, PHC3, DRC6, CBPC3, NAV1, VP37A, KMT2C, ZMIZ2, BD1L1, ARI1B, FLCN, NUP35, TOIP2, TNIP2, KNL1, OR2L2, PUM2, CC110, TBC15, STT3B, ZN507, ALMS1, DLG5, KCNV2, BRX1, DOT1L, GEMI5, PARD3, ZN384, SMAP2, IASPP, TM263, ZFN2B, NUDC2, PCNP, TRUB1, LMO7, ATX2L, PALLD, P66B, BBX, ZCH14, GBF1, SMG7, RTF1, NICA, PHF3, MAML1, ZN592, LAR4B, TFG, TAF4B, RREB1, SC65, CBP, SYMPK, DDX17, GPKOW, FUBP2, UBP7, LPP, LSM10, NCLN, MRTFA, FUBP1, TTC17, PBIP1, TTC28, TOM6, PF21A, INT12, REPS1, ESS2, MBD6, ELP4, SGF29, RBM33, ZN503, P121A, TONSL, PDLI5, ERO1A, DOCK6, FUBP3, RSRC1, ZN594, VCIP1, ZN462, LCOR, PDLI2, CLP1L, Z512B, ZFR, EP400, MRFL, H6ST2, TIGD1, NOL4L, DOCK7, RPR1A, RBM14, ADCYA, QKI, LENG8, TRNT1, PP1RA, PHF12, CIC, MED15, ERBIN, HMCN1, LMF1, PIGS, WRIP1, SIN3A, MINT, HTF4, EYA3, POP1, TEAD3, TTC1, CSN8, ATX2, ARI3A, ANM1, PKP2, TEP1, DPH2, WAC, DIDO1, HNRL1, RBM4, SSBP4, PRR14, SSBP3, YTHD1, KPCD2, ZCHC2, TB182, AMRA1, CE295, TANC1, ZC12C, CEP44, STRAB, SP130, BRD8, RGAP1, SMG9, APC1, I2BPL, TMX4, KI13A, WDR13, EPC1, ADNP, ZN106, TM245, FOXP1, PABP3, WNK1, E41L1, ZHX3, BICC1, PEAK1, PPR3E, ZN703, PKHA5, CLSPN, BCDO1, RC3H2, ZFYV1, TAF9B, EMAL4, ZBT20, NCOA5, TANC2, ZN532, NCK5L, TNR6C, CHD8, FBSL, APMAP, DMAP1, UBN1, DCP1A, INCE, ANLN, GEPH, PDLI7, TULP4, HOME2, SLX9, DIAP3, BMP2K, RBM12, STAU2, DDX28, CWC25, CARF, ETAA1, ABI2, HXC10, BCLF1, TAB2, CELR3, CDK12, GRHL1, SACS, ITSN2, BICRA, CNOT2, TMEM9, CAC1I, CAMP3, DAPLE, RCC2, DIP2B, MBD5, CT2NL, F135A, KANL3, RERE, SE1L1, TRM7, YM012, KDM5B, LIMD1, TCF20, SUN2, LIMA1, SEPT9, UBQL2, TRPS1, S30BP, NRBP, BAZ2B, SIX4, HOOK1, CDC23, TASOR, GMEB2, TNIK, PARP4, NUP50, ZHX1, CDV3, MCTS1, KCNH3, LRFN2, MRTFB, ZBT21, PRR12, YETS2, HECD1, ZMYD8, NOTC3, SPAT2, SOX13, G3BP2, MAGD2, MINP1, MACF1, CP131, SCAF8, TRI33, PHF8, LIMC1, TNR6B, SRRM2, SCML2, ZN148, POLH, INVS, ICE1, R3HD2, MAN1, TR150, WBP11, ZN281, STA13, WNK2, ARIP4, MTCL1, DCAF1, RPGF2, IRS2, CRBG1, HYOU1, SAM50, PRC2C, YTHD2, NCOR2, GMEB1, DC1L1, EPN1, NCOA3, ZHX2, S23IP, U3KPZ7, V9GYH0
Species: Homo sapiens
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Song H, Ma J, Bian Z, Chen S, Zhu J, Wang J, Huang N, Yin M, Sun F, Xu M, Pan Q. Global profiling of O-GlcNAcylated and/or phosphorylated proteins in hepatoblastoma. Signal transduction and targeted therapy 2019 4 31637018
Abstract:
O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) and phosphorylation are critical posttranslational modifications that are involved in regulating the functions of proteins involved in tumorigenesis and the development of various solid tumors. However, a detailed characterization of the patterns of these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children, has not been performed. Here, we examined O-GlcNAc-modified or phospho-modified peptides and proteins in HB through quantitative proteomic analysis of HB tissues and paired normal liver tissues. Our results identified 114 O-GlcNAcylated peptides belonging to 78 proteins and 3494 phosphorylated peptides in 2088 proteins. Interestingly, 41 proteins were modified by both O-GlcNAcylation and phosphorylation. These proteins are involved in multiple molecular and cellular processes, including chromatin remodeling, transcription, translation, transportation, and organelle organization. In addition, we verified the accuracy of the proteomics results and found a competitive inhibitory effect between O-GlcNAcylation and phosphorylation of HSPB1. Further, O-GlcNAcylation modification of HSPB1 promoted proliferation and enhanced the chemotherapeutic resistance of HB cell lines in vitro. Collectively, our research suggests that O-GlcNAc-modified and/or phospho-modified proteins may play a crucial role in the pathogenesis of HB.
Species: Homo sapiens
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Malaker SA, Penny SA, Steadman LG, Myers PT, Loke JC, Raghavan M, Bai DL, Shabanowitz J, Hunt DF, Cobbold M. Identification of Glycopeptides as Posttranslationally Modified Neoantigens in Leukemia. Cancer immunology research 2017 5(5) 28314751
Abstract:
Leukemias are highly immunogenic, but they have a low mutational load, providing few mutated peptide targets. Thus, the identification of alternative neoantigens is a pressing need. Here, we identify 36 MHC class I-associated peptide antigens with O-linked β-N-acetylglucosamine (O-GlcNAc) modifications as candidate neoantigens, using three experimental approaches. Thirteen of these peptides were also detected with disaccharide units on the same residues and two contain either mono- and/or di-methylated arginine residues. A subset were linked with key cancer pathways, and these peptides were shared across all of the leukemia patient samples tested (5/5). Seven of the O-GlcNAc peptides were synthesized and five (71%) were shown to be associated with multifunctional memory T-cell responses in healthy donors. An O-GlcNAc-specific T-cell line specifically killed autologous cells pulsed with the modified peptide, but not the equivalent unmodified peptide. Therefore, these posttranslationally modified neoantigens provide logical targets for cancer immunotherapy. Cancer Immunol Res; 5(5); 376-84. ©2017 AACR.
Species: Homo sapiens
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