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Jeon BC, Kim YJ, Park AK, Song MR, Na KM, Lee J, An D, Park Y, Hwang H, Kim TD, Lim J, Park SK. Dynamic O-GlcNAcylation governs long-range chromatin interactions in V(D)J recombination during early B-cell development. Cellular & molecular immunology 2025 22(1) 39627609
Abstract:
V(D)J recombination secures the production of functional immunoglobulin (Ig) genes and antibody diversity during the early stages of B-cell development through long-distance interactions mediated by cis-regulatory elements and trans-acting factors. O-GlcNAcylation is a dynamic and reversible posttranslational modification of nuclear and cytoplasmic proteins that regulates various protein functions, including DNA-binding affinity and protein-protein interactions. However, the effects of O-GlcNAcylation on proteins involved in V(D)J recombination remain largely unknown. To elucidate this relationship, we downregulated O-GlcNAcylation in a mouse model by administering an O-GlcNAc inhibitor or restricting the consumption of a regular diet. Interestingly, the inhibition of O-GlcNAcylation in mice severely impaired Ig heavy-chain (IgH) gene rearrangement. We identified several factors crucial for V(D)J recombination, including YY1, CTCF, SMC1, and SMC3, as direct targets of O-GlcNAc modification. Importantly, O-GlcNAcylation regulates the physical interaction between SMC1 and SMC3 and the DNA-binding patterns of YY1 at the IgH gene locus. Moreover, O-GlcNAc inhibition downregulated DDX5 protein expression, affecting the functional association of CTCF with its DNA-binding sites at the IgH locus. Our results showed that locus contraction and long-range interactions throughout the IgH locus are disrupted in a manner dependent on the cellular O-GlcNAc level. In this study, we established that V(D)J recombination relies on the O-GlcNAc status of stage-specific proteins during early B-cell development and identified O-GlcNAc-dependent mechanisms as new regulatory components for the development of a diverse antibody repertoire.
O-GlcNAc proteins:
MPEG1, CUL4B, DHX8, RHG27, VIR, PNISR, FRPD1, RENT2, LAS1L, ITIH4, THOC2, MMRN1, PYR1, YTDC2, PTPRB, ANR44, RBM25, OSBL8, DAAF5, SAFB1, KI67, DESP, YTDC1, UBE4A, NUMA1, MORC3, HXK2, LEG9, KNG1, UBE3A, DCTN1, DIAP1, U5S1, RL21, PHB2, CPSF2, DHX15, EXOC4, STAG2, AP1B1, PININ, HNRH1, SP100, GP1BA, ITB3, RL35A, SPT5H, DHX9, E41L2, BAZ1A, ZFR, ROA2, PRS6A, FA5, AFAM, COR1A, SP1, C1QR1, COX2, AMY1, CO3, CO4B, B2MG, HBA, HBB1, K1C10, K2C1, CFAB, ALDOA, TBA1B, TBA3, ITAM, K1C18, LDHA, LCK, APOA4, PTPRC, CFAH, TTHY, ANXA2, ALBU, A1AT1, SPA3K, HS90A, TRFL, ENPL, APOE, MDHM, GNAI2, RPB1, ITB1, PDIA1, NUCL, APOA2, PTPRQ, CALM2, EF1A1, 4F2, PARP1, PERM, FINC, HS90B, K2C8, ITA5, ITB2, TCPA, RL7A, GELS, ICAM1, DNMT1, S10A6, RL27A, RS16, RL7, RSSA, LMNB1, ANXA6, RLA0, CD44, LEUK, H12, CN37, AMPE, HS71L, G3P, LAMP2, HSP72, ENOA, PTBP1, PPIA, TPIS, LYZ1, PCNA, PTPRA, BASI, KS6A1, KS6A3, COF1, FAS, THRB, RL13A, BIP, VIME, PLMN, VTDB, A1AT2, CBL, AP1G1, EIF3A, EST1C, ITAL, CD11B, MCM3, RS2, CD19, UBF1, TLN1, EZRI, MOES, KLKB1, H2AX, VAV, NCKP1, MUG1, KIF2A, DPP4, PTN6, FETUA, C5AR1, CEAM1, CD68, ANT3, SYWC, KIF4, DPOLA, RAB5C, RAB18, CD22, TSP1, CALX, RFC1, PRDX1, RL12, RL18, DNLI1, GRP75, DYN2, RL28, MMP9, STAT1, STA5B, EPS15, TCPQ, MSH2, H14, H15, RAGP1, SIPA1, NSF, PRS7, BRCC3, NEDD4, CAPZB, RL6, RL5, RL13, RL36, KSYK, PERE, ROA1, MCM4, MCM5, SAHH, K2C6A, VATA, PA2G4, RAB7A, RL9, ADT2, IMA1, PON1, DPOD1, UBP10, KPYM, STAT6, RL10A, CEBPZ, PIPNB, MSH6, UBP5, ATPB, UBP25, NICA, ACTN4, EF2, OPA1, FOXP1, TPM2, WDHD1, ARPC4, RUVB1, PCBP1, ACTB, IF4A1, RS20, UB2D3, ARF3, RL26, RL27, RL37A, ARF4, HNRPK, RS7, PRS4, RS8, RS15A, RS14, RS23, RS18, RS11, RS13, SMD2, ARF6, PRS10, RS4X, RL18A, RL23A, RS6, H4, VATB2, RAB1A, RAN, RL23, RS24, RS25, RS26, RL30, RL31, RS3, RL8, PROF1, RL40, HSP7C, PHB1, RL22, RACK1, ACTS, TBA4A, TBB4B, 1433F, IMB1, M4K1, PKN1, STIM1, PYRG2, ROCK1, RAD50, PYRG1, TCPH, TCPB, TCPD, TCPE, TCPZ, TCPG, WNK1, RHOG, RL19, H33, BACH2, MCM2, MCM6, RS3A, ANX11, SMRC1, FUMH, ARVC, TBB5, APOA1, A1AT4, TYY1, HNRL2, LYAM3, TOP2A, APOH, TERA, UBA1, PLAK, ATPA, IKZF1, SPA3M, SMRCD, TOP1, RAC2, PYC, IF2P, CBG, ACADS, AMBP, PECA1, SSRP1, ZCH18, K2C80, PSA, PTCD3, NSUN2, EDEM3, MCM9, TMC5, HMHA1, HP1B3, GUAA, H2AV, SMCA4, PRC2C, MIDN, K1C26, K22E, PSMD1, BRE1B, ESYT1, AAK1, RHG17, EDC4, UBP19, GPD1L, ELNE, SC31A, IQGA2, K22O, ITB2L, C1TM, UN13A, PLCH1, PDS5B, CENPJ, DDX46, TR150, A16A1, EHMT1, MCTP2, RBM27, CYFP2, PSME4, MYO1G, LC7L3, PUR4, MYH1, LEO1, SIN3A, XRCC1, ODO1, HNRPD, SAMH1, HELLS, ARHG2, I17RA, PML, 2A5G, PPM1G, CFAI, CERU, CTCF, PRDX2, EZH2, HCFC1, PA1B3, ARHG1, PLSL, A2AP, HSP74, DSG1A, GSLG1, EWS, RAD21, FSCN1, GDIB, DDX5, HS105, ITIH2, ITA6, EI2BD, SERA, KINH, PDCD4, PZP, PRG2, MYH10, MCM7, NPM, PCBP2, CTR9, DDX3X, CD180, SPTB2, SPR1A, TIF1B, TFR1, RU17, SPT6H, NDUA4, IF4G2, MINT, RHG30, H2B1B, TOP2B, TPP2, AT2A3, H2A2C, VINC, PUR2, CLH1, SYMC, GNPTA, PDS5A, CDC5L, CE290, F120A, UBP7, JADE3, K1C42, K2C72, SR140, K2C73, S23IP, IF4G1, RBM26, P4R3A, U520, ABCF1, SMHD1, UGGG1, XPO1, ANO6, KIF15, KIF11, FHOD1, FKB15, PTN23, LPPRC, SMRC2, ECM29, CHD4, PK3C3, NUP98, GMIP, NFRKB, TEX2, UBE2O, KDM3B, CE162, CNOT1, CAND1, LARP1, VIP2, RS9, RL35, RS27L, 2AAA, SND1, ASAP2, IPO8, HUWE1, LC7L2, MBB1A, INT7, CTDP1, PP6R1, ELP1, DCAF1, CLAP1, SCRIB, PUM1, NU214, NAA15, FACD2, FBLL1, UBP2L, SYMPK, SIG10, DDX42, ANFY1, EFTU, TNPO1, ROA3, PLD4, SYAC, S2512, NU107, PTBP3, NRDC, ERC6L, GANAB, SP130, NUP93, SUN2, RCC2, IPO5, EMSY, ODP2, RBGPR, SYLC, SYQ, ECHA, RL24, CLAP2, CNDH2, PB1, FLNA, SYIC, IFIX, CIP2A, GEMI5, UBP47, CTL2, TBCD, POGZ, ANC2, KS6A5, EFL1, LCAP, DOCK8, CND2, IWS1, RBM14, DOCK2, UBA6, MIC60, UFL1, VCIP1, NUP88, NED4L, RPB2, AQR, SMC4, SMC2, SYEP, TCRG1, LONM, OGT1, CHERP, CCAR1, INT5, PYGB, COPA, PLCG2, INT4, EIF3B, BCLF1, K319L, URP2, DNM1L, NEK9, FCHO1, PAF1, IPO11, CND1, MATR3, PLCL2, DP13A, PO121, SF3A1, HNRPL, NU133, EIF3C, BST2, CD177, ADIPL, CDC16, STPAP, LRC8C, ACSF2, EVI2B, MYH9, UHRF1, VIGLN, ADPGK, PSMD2, HNRL1, AT1A1, MICA1, CCAR2, DX39A, SRSF4, K2C79, RFA1, HNRPU, S25A3, RBM39, SEC63, IPO4, SFPQ, ACLY, IF4A3, NDUS1, ATPG, DDX1, UBAP2, HEMO, IPO9, RBM5, PRP6, SMCA5, SP16H, TADBP, SF3B3, SYDC, PP6R3, C1TC, NOP2, PDE2A, KIF2C, K2C5, SIR1, XPO5, SMRD2, ECHB, ARP3, EMIL1, UN45A, ACON, DPP3, HSP7E, GTPB4, ARBK1, SRRT, SF3B1, NU155, RRBP1, DHX30, RL17, NUDC2, 6PGL, COTL1, RM18, TRAP1, AT5F1, RL14, XPOT, PRPS2, RRP44, SMC1A, SMUF1, SMC3, PUR9, SNX2, ROA0, RL11, GARS, RL15, MTREX, MMS19, HNRPM, SYRC, NH2L1, RL34, GRIFN, UB2V2, S10AE, CORO7, STAG1, CUL5, SC23B, CALL3, NOP56, RL4, EF1G, PRP4, QCR2, PELP1, AP2B1, XRN2, NVL, EIF3K, 6PGD, SYF1, EIF3F, XPO7, IPO7, RENT1, BCAP, PESC, ERAP1, VPS35, EHD4, TFP11, XPO2, PKHA2, RBP2, UBE4B, SHIP1, HRG, XPO4, AN32B, GTF2I, DYHC1, STK4, COPB, DDX21, ACINU, FLII, IQGA1, HYOU1, HIP1R, FMNL1, SACS, SART3, GIT2, MY18A, ITA2B, FAK2, CAF1A, K1C17, FETUB, PLEC, PO210, ADDA, PCLO, COPG1, UBQL2, H2AY, ZEB2, GALK1, SC11A, MTA2, PR40A, TIM, MYO1C, INSRR, MD1L1, PDC6I, PFKAP, CXA10, GANP, IF2G, ADNP, P5CS, SAE2, ARI1, DX39B, CLIC1, SYVC, AP3B1, ILF3, USO1, HNRPC, BAZ1B, K1C16, SNUT1
Species: Mus musculus
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Narayanan B, Zahra F, Reeves RA, Aggarwal A, O'Meally RN, Henry RK, Craven M, Jacobson A, Cole RN, Kohr MJ, Umapathi P, Zachara NE. Differential Detection of O-GlcNAcylated proteins in the heart using antibodies. Analytical biochemistry 2023 678 37507081
Abstract:
Thousands of mammalian intracellular proteins are dynamically modified by O-linked β-N-acetylglucosamine (O-GlcNAc). Global changes in O-GlcNAcylation have been associated with the development of cardiomyopathy, heart failure, hypertension, and neurodegenerative disease. Levels of O-GlcNAc in cells and tissues can be detected using numerous approaches; however, immunoblotting using GlcNAc-specific antibodies and lectins is commonplace. The goal of this study was to optimize the detection of O-GlcNAc in heart lysates by immunoblotting. Using a combination of tissue fractionation, immunoblotting, and galactosyltransferase labeling, as well as hearts from wild-type and O-GlcNAc transferase transgenic mice, we demonstrate that contractile proteins in the heart are differentially detected by two commercially available antibodies (CTD110.6 and RL2). As CTD110.6 displays poor reactivity toward contractile proteins, and as these proteins represent a major fraction of the heart proteome, a better assessment of cardiac O-GlcNAcylation is obtained in total tissue lysates with RL2. The data presented highlight tissue lysis approaches that should aid the assessment of the cardiac O-GlcNAcylation by immunoblotting.
O-GlcNAc proteins:
A0A023T778, A0A075B5P3, A0A075B5P4, A0A075B5P6, A0A075B5T2, A0A075B5T7, A0A087WP81, A0A087WPL5, A0A087WR50, A0A087WS16, A0A087WS46, A0A087WSC6, A0A0A0MQ79, A0A0A0MQA5, A0A0A0MQD2, A0A0A0MQF6, A0A0A0MQJ4, A0A0A0MQM0, A0A0A6YVU8, A0A0A6YW67, A0A0A6YW80, A0A0A6YWP6, A0A0A6YX26, A0A0A6YXF6, A0A0A6YXH3, A0A0A6YXV1, A0A0B4J1E7, A0A0B4J1H7, A0A0F6AIX5, A0A0G2JDI9, A0A0G2JDL9, A0A0G2JDR9, GBP6, A0A0G2JDW2, A0A0G2JE25, A0A0G2JEP0, A0A0G2JEX1, A0A0G2JEY6, A0A0G2JF52, A0A0G2JF85, A0A0G2JG74, A0A0G2JGJ1, A0A0G2JGS0, A0A0J9YU07, A0A0J9YU24, A0A0J9YUZ4, A0A0M3HEQ0, A0A0N4SV40, A0A0N4SV66, A0A0N4SVB1, A0A0N4SVB8, A0A0N4SVK8, A0A0N4SVL9, A0A0N4SW07, A0A0R4J023, A0A0R4J038, A0A0R4J050, A0A0R4J052, A0A0R4J093, A0A0R4J0H8, A0A0R4J0I1, A0A0R4J0K2, A0A0R4J0L5, A0A0R4J0L6, A0A0R4J0S3, A0A0R4J0T5, A0A0R4J0X5, A0A0R4J0Z1, A0A0R4J138, A0A0R4J196, A0A0R4J1E2, A0A0R4J1J3, A0A0R4J1Q6, A0A0R4J1R7, A0A0R4J1W0, A0A0R4J1W7, A0A0R4J260, A0A0R4J275, A0A0U1RPW2, A0A0U1RPY8, A0A140LHG8, A0A140LIU4, A0A140LIZ5, A0A140LJ98, A0A140LJB7, A0A171EBL2, A0A1B0GQU8, A0A1B0GR11, A0A1B0GRP7, A0A1B0GRV0, A0A1B0GRV3, A0A1B0GRW3, A0A1B0GS58, A0A1B0GS68, A0A1B0GS70, A0A1B0GS91, A0A1B0GSG5, A0A1B0GSK8, A0A1B0GSR9, A0A1B0GX27, A0A1C7CYV0, A0A1C7ZN10, A0A1D5RM79, A0A1L1SQ51, A0A1L1SQA8, A0A1L1SS27, A0A1L1SST0, A0A1L1STE6, A0A1L1SV25, A0A1L1SV73, A0A1W2P6E6, A0A1W2P6P1, A0A1W2P768, A0A1W2P7A1, A0A1W2P812, A0A1Y7VJY8, A0A1Y7VKT9, A0A1Y7VKY1, A0A1Y7VLP0, A0A286YCI8, A0A286YCS6, A0A286YD12, A0A286YDA2, A0A2I3BPW0, A0A2I3BQE3, A0A2I3BQF4, A0A2I3BRL8, A0A2K6EDJ7, A0A2R8VHF9, A0A2R8VHX0, A0A338P6D9, A0A338P6G0, A0A338P6N4, A0A338P703, A0A338P731, A0A338P786, A0A338P7D7, A0A338P7F1, A0A338P7G4, A0A3B2W824, A0A3B2WB97, A0A3B2WBC6, A0A3B2WCN9, A0A3Q4EBV4, A0A3Q4EG54, A0A3Q4EH93, A0A3Q4EI56, A0A494B908, A0A494B923, A0A494B955, A0A494B985, A0A494B9D8, A0A494B9P3, A0A494B9W3, A0A494B9X1, A0A494B9Y4, A0A494BA51, A0A494BAJ6, A0A494BB38, A0A494BBC1, A0A494BBG8, A0A571BEC9, A0A571BEG4, A0A571BG59, A0A571BGD8, A0A5F8MPB9, A0A5F8MPD6, A0A5F8MPK9, A0A5F8MPM4, A0A5F8MPN8, A0A5F8MPW1, A0A5F8MPY2, A0A5K1VVQ9, A0A668KL51, A0A668KLD3, A0A6I8MWZ8, A0A6I8MX27, A1BN54, A2A513, A2A5F5, A2A6F8, A2A6Q8, A2A7A7, A2A813, A2A848, TM201, A2A997, A2A9Q2, OBSCN, A2AAW9, A2AE89, A2AEX6, A2AFQ0, A2AFQ2, A2AGJ9, A2AI69, A2AI87, NDUF6, A2AIM4, A2AIW9, A2AK42, A2AKD7, A2AKU9, A2AKV9, A2AL12, A2ALV7, CAVN4, A2AMW0, UBR4, A2AN84, A2APD7, A2AQN4, MYH7B, A2AQR0, A2AQY8, A2AS98, TITIN, A2AT02, A2AU61, A2AUD5, RBGP1, A2BDW0, A2BH06, A2BI12, A2CEK3, A2CES4, A2CG35, A3KFU5, A3KGU5, ARMT1, A6X925, A8DUK4, A8JYK8, CISD3, B1AR28, B1AR93, B1ARA3, B1ASE2, B1ASZ3, B1AT10, B1AU25, B1AUX2, B1AV14, B1AXW5, B1AZ14, B1B0C7, B2C3G8, GNAI1, B2RXT3, B2RY24, B7FAU9, B7ZCI2, B8JJI4, B8JJM5, B8JK32, B9EIZ7, D3YTL5, D3YU39, D3YUG3, D3YUK5, D3YUM1, D3YUP1, D3YVF4, D3YVI6, D3YVV9, D3YW19, D3YWA4, D3YX99, D3YXT0, D3YY36, D3YYE1, D3YYG9, D3YYS6, D3YZ06, D3YZ71, D3Z041, D3Z067, D3Z0G0, D3Z0X5, D3Z0Y2, D3Z1B5, D3Z1V4, D3Z263, D3Z2B3, D3Z2Y8, D3Z4A4, D3Z5K6, D3Z5W3, D3Z627, D3Z636, D3Z6F5, D3Z780, D3Z7A7, D3Z7D5, D3Z7K3, D3Z7U0, D3Z7V3, D5MCW4, D6REH1, D6RFU2, D6RFU9, D6RGM3, D6RH37, E0CXB1, E0CXH2, E0CXN7, E0CXS3, E0CY23, E0CZ90, E0CZE0, E9PUD2, E9PUE8, E9PUM3, E9PUU2, E9PUY9, E9PV12, FIBA, E9PV63, E9PV66, E9PVP0, E9PVU0, E9PWE8, E9PX89, E9PYF1, E9PYI8, E9PZ00, E9PZ88, E9PZC4, E9PZD8, E9PZF0, E9PZI9, E9PZP8, E9Q133, E9Q1J7, E9Q1T9, E9Q1V0, E9Q264, RYR2, E9Q4T8, ACACB, DESP, E9Q5B5, E9Q5I9, E9Q616, E9Q6A9, E9Q6C2, E9Q6W2, E9Q7A5, E9Q800, E9Q933, E9Q9C0, E9Q9T8, E9QJV4, E9QKY4, E9QL13, E9QN70, E9QPD7, E9QPX3, F6QPR1, F6QYE1, F6QYF8, F6RR81, F6VVE6, F6VVY4, F6VY18, F6XI62, F6YCA7, F6ZV59, F7A3N3, F7DBQ0, SKI3, F8VPN4, F8VQJ3, F8WGL3, F8WHU8, F8WIB1, F8WIE5, F8WIT2, F8WIV2, F8WIV5, F8WJ05, G3UVU2, G3UVV4, G3UW30, G3UW85, G3UWN9, G3UX26, G3UXI6, G3UXX3, G3UYR8, G3UZ33, G3UZ48, G3X8R0, G3X8R1, G3X8T3, G3X8T9, QNG1, G3X956, G3X975, G3X977, G3X983, G3X9Q1, G3X9U9, G3XA48, G5DDB7, G5E823, G5E839, G5E883, G5E8R7, H3BIY9, H3BJI5, H3BJP9, H3BJQ7, H3BKH4, H3BKH6, H3BL49, H3BLH2, H7BWZ3, H7BX01, H7BX88, H7BX99, I7HLV2, J3QMG3, J3QPW1, J3QPZ9, J3QQ13, K3W4R2, K3W4S6, K4DI63, L7N451, M0QWU8, CAN2, DPYL2, DLDH, GSTO1, RL21, AMACR, SCRB2, PSMD4, ECH1, ANXA3, C1QBP, TIM44, AL1A7, CAVN1, SYUA, IMPCT, DSG2, NIPS2, AT2A2, PGAM2, PDLI1, AOC3, FHL2, PSA3, DHB12, WDR1, MTX2, ROA2, COMT, BIRC6, IDHC, GNPI1, KBL, AFAM, C1QR1, LANC1, ADH1, COX1, CAH2, CO3, CO4B, HBE, NU1M, NU4M, NU5M, FABP4, MYG, ALDOA, KAPCA, AATC, AATM, TBA1B, CO5, G6PI, MAOX, TTHY, KCRM, ANXA2, ALBU, K2C4, HS90A, CBR2, ENPL, MDHM, PDIA1, NUCL, PGK1, FRIH, SODM, H2AZ, IFI5B, ANXA1, EF1A1, NID1, CATB, THIO, RRAS, H2B1M, H10, LIPL, FABPH, HS90B, DMD, K2C8, ITPR1, TCPA, UCP1, PFKAL, RL7A, GELS, CAH1, GPDA, AT1B1, RS16, RSSA, CALR, HA2B, PSMD3, LMNB1, GLNA, PMGE, CAH3, LEG1, LEG3, CN37, DDX3L, AMPE, ENOA, SBP1, TPIS, CATD, FAS, SERPH, COX41, BIP, PRDX3, VIME, PLMN, ENOB, VTDB, TGM2, AP1G1, EIF3A, CXA1, CRYAB, EST1C, CATA, PPIB, GSTA4, LKHA4, AL1A1, RS2, LYN, TLN1, EZRI, MOES, CTNA1, PTMA, DHE3, PSMD7, FKB1A, PDIA3, ACOHC, ADHX, PGS1, PGS2, NP1L1, ATX10, MUG1, OAT, FKBP4, HMGB2, DESM, MP2K1, SCP2, LA, ANT3, SYWC, MIF, RAB21, HSPB7, TSP1, ODPA, CALX, RL12, PPM1B, TAGL, HMGCL, GRP75, CAP1, TKT, VP26A, INMT, ECI1, H14, ALDR, ALD2, COF2, ACADM, NSF, VPS4B, PRS7, RB11B, NEDD4, PA24A, ALDH2, GSHR, MK14, PFKAM, RL6, ANXA5, ABCD1, LMNA, CBR1, COX8B, TNNI3, ADT1, HEP2, ROA1, INPP, MCM4, CAV1, SAHH, FMO1, GDIA, CSRP3, VATA, ACADL, DHB4, MLRV, HDGF, ADT2, THTR, PON1, KPYM, NDUS6, CPT2, ODB2, IDHP, RD23A, PUR8, DDX6, ADK, ACYP2, AP4A, CX6B1, UBP5, ATPB, CD38, ERP29, EF2, TPM1, B2L13, RUVB1, EIF3E, PCBP1, NPL4, ACTB, CDC42, IF4A1, UBC12, UBE2N, ARP2, ARF3, RL27, 1433G, RRAS2, RS7, PP1B, RS8, RS15A, 1433E, RS23, SMD3, EF1A2, RS4X, AP2S1, RS6, H4, RAN, RS24, RS26, CYC, RL32, FBX40, PROF1, LIS1, HSP7C, TCTP, CH60, IF4E, 1433Z, RS17, PHB1, ACTC, RACK1, 1433T, TBB4B, 1433F, USP9X, IDHG1, NACAM, F16P2, DCUP, PYRG1, TCPB, TCPE, TCPZ, ARF5, AP2M1, RL19, ISC2A, CSRP1, NRP1, RS3A, CPT1A, WBP2, FUMH, LAMA4, TBB5, G6PD1, APOA1, A1AT5, APOH, TERA, UBA1, PLAK, MYH6, KCRB, CO6A1, FABP5, ATP5I, CBG, MPRI, ACADS, AMBP, CD36, Q14BI5, ACSS3, A1BG, TRI72, Q20BD0, NLR1A, HSDL2, OSBP1, CUL4A, Q3TG45, Q3TGM7, GUAA, TM38A, Q3TXN1, PSMD1, SC31B, SYRM, DDB1, Q3U2G2, Q3U422, Q3U816, Q3U8Y1, Q3UER8, Q3UF75, TM10C, Q3UGX2, HAP28, MYLK3, Q3UJQ9, GPD1L, PP1R7, HDGR2, SC31A, THEM4, Q3UZJ4, ST1D1, Q3V117, HSPB6, D39U1, Q5SQ27, Q5SQB0, Q5SUS9, Q5SWN2, ACACA, MYH4, MYH1, COPD, A1AG1, ODO1, LAMA2, STIP1, VDAC1, COQ8A, ADIPO, 2A5G, LAMA5, HARS1, HCDH, GDIB, HS105, SERA, PZP, MIME, POSTN, PON3, DAG1, MYOM1, SPTB2, TX261, TIF1B, TSN, TFR1, NDUA4, CYTB, CAVN2, BTF3, CH10, ADH7, CP4B1, TOP2B, TPP2, H2A2B, H2A2C, NQO1, VINC, PUR2, CTNA3, CLH1, RFTN1, NOMO1, K2C73, 2ABA, U520, XPO1, KCRS, Q6P8N8, OXSR1, LPPRC, UBR2, CAND1, CAND2, MLEC, RS9, IF2A, KAT3, 2AAA, ATPMK, Q7TNL5, SRCA, ELP1, SESD1, FLNB, PANK4, IREB2, EFTU, MIRO1, SAM50, S2540, SYAC, SYNM, F210A, S2512, F13A, EHD2, ECHM, SYIM, AHSA1, RCC2, IPO5, ODPX, MAON, ODP2, ECHA, PPA6, Q8BRB6, AAPK2, Q8BTS3, CSN7B, PPME1, NUDT9, AOFB, SSDH, THIM, KANK2, VP13C, COMD2, PGM5, NHLC2, GPCP1, ASGL1, LCAP, EXOG, THOP1, Q8C483, EMC1, Q8C845, Q8C8G3, ANK2, VWA8, ARK72, SYEP, LONM, UN45B, BICRL, PGP, FBX4, AL4A1, PDLI5, DI3L2, PYGB, FERM2, COPA, PAK2, HMCS1, ACAD9, MIRO2, AFG32, EIF3B, ACSL5, FIBB, TACO1, PDXK, COQ9, SDHA, FMO2, LZIC, HIBCH, THIL, ERF3A, SUOX, FAHD1, S2542, EIF3C, CMBL, COQ6, Q8R2P8, FABD, GBRL1, CLYBL, TMC2, UBP15, RMC1, MAVS, EST1D, ACSF2, CK068, SYLM, MYH9, PPCS, HNRL1, AT1A1, LMCD1, HNRPU, S25A3, RBM39, FLNC, ETFR1, Q91VB8, NDUS1, HNMT, DDX1, CBR4, EIF3H, CISD1, HEMO, VPS36, RHG35, FAKD4, L2HDH, RPN1, TWF1, MYH7, PCCA, UGPA, SMCA5, HNRLL, ETFD, TRFE, RHEB, MACD1, SYDC, MPI, RT02, CPT1B, DCMC, SMRD2, EIF3M, ECHB, Q99JZ4, RRAGC, VMA5A, ACON, DCTN2, NAMPT, PPIF, DHRS1, 3HIDH, DHRS4, MAT2B, NDUAA, ETFA, DDAH2, RTCB, GRPE1, NDUS5, DNJA3, ASPN, MCCA, PPR3A, RM09, ACS2L, NUDT7, RTN4, GDIR1, PRP8, NDUA5, COX6C, ATP5L, LGUL, AMPL, MYL9, NDUC2, DECR, MTAP, PKP2, NDUA2, SDHB, NDUB4, TM223, COTL1, NDUB9, TXD17, TRAP1, AT5F1, ACO13, 1433B, DPH2, M2OM, CHSP1, NAR4, TPPP3, MIC19, SMC1A, NUD17, PUR9, SNX2, CYGB, ROA0, COQ5, MITOS, MPPB, CYBP, BIEA, QCR1, HS12B, RL15, GLYM, EFTS, AL1B1, CISY, 5NT3A, ODPB, SYRC, EXOS7, CY1, SYTC, HINT2, ILEUA, GAL3A, HHATL, RM53, ODO2, OXSM, CUL2, EFHD1, PLCC, NDUV2, FUND2, F162A, ECHD3, IPYR, QCR7, ITPA, RL4, EF1G, T126A, PHP14, MTU1, ATPO, QCR2, PLIN3, LMAN2, PGAM1, ACDSB, OCTC, RT15, 6PGD, NDUA8, PUR6, GSTK1, MECR, NDUBA, NDUS3, CRIP2, RMD1, ETFB, LACTB, DHB11, MMSA, ERAP1, VPS35, RM46, EHD4, PARVB, M3K20, PSMG2, PYGL, IVD, DYHC1, NQO2, ACTN2, COPB, AK1A1, DDX21, RL38, SH3L1, PROF2, TBA8, PRELP, IQGA1, HYOU1, LDB3, GLTP, PALS2, PPCE, MLRA, DRG2, PLEC, S2513, TOM40, CLIC4, DNJA2, ACOT2, AAKB1, DEST, ACOT9, KAD1, PSA4, PSB3, PSB2, SAE1, BMP10, MYO1C, KAD2, KAD3, CUL1, PDC6I, COR1C, SUCA, KAD4, CATZ, ABEC2, CBPQ, EHD1, S12A7, GRK1, MTNB, GBP2, SYUG, TWF2, NFS1, NDUA7, CLIC1, STK39, MTMR9, SUCB2, SUCB1, PCKGC, PSD10, MCAT, S4R1F2, S4R1N1, S4R242
Species: Mus musculus
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Lee BE, Kim HY, Kim HJ, Jeong H, Kim BG, Lee HE, Lee J, Kim HB, Lee SE, Yang YR, Yi EC, Hanover JA, Myung K, Suh PG, Kwon T, Kim JI. O-GlcNAcylation regulates dopamine neuron function, survival and degeneration in Parkinson disease. Brain : a journal of neurology 2020 143(12) 33300544
Abstract:
The dopamine system in the midbrain is essential for volitional movement, action selection, and reward-related learning. Despite its versatile roles, it contains only a small set of neurons in the brainstem. These dopamine neurons are especially susceptible to Parkinson's disease and prematurely degenerate in the course of disease progression, while the discovery of new therapeutic interventions has been disappointingly unsuccessful. Here, we show that O-GlcNAcylation, an essential post-translational modification in various types of cells, is critical for the physiological function and survival of dopamine neurons. Bidirectional modulation of O-GlcNAcylation importantly regulates dopamine neurons at the molecular, synaptic, cellular, and behavioural levels. Remarkably, genetic and pharmacological upregulation of O-GlcNAcylation mitigates neurodegeneration, synaptic impairments, and motor deficits in an animal model of Parkinson's disease. These findings provide insights into the functional importance of O-GlcNAcylation in the dopamine system, which may be utilized to protect dopamine neurons against Parkinson's disease pathology.
O-GlcNAc proteins:
BIG2, F1712, VIR, AJM1, RPGP1, UBR4, SCN1A, AGRIN, KALRN, STPG3, FXL16, TT23L, PTPRS, GRIK3, SCN2A, DLGP4, OSBL8, PTPRZ, PGBD5, GLSK, GCN1, CE350, PI4KA, RYR2, AGRF2, UBE4A, NRX2A, FRY, SYGP1, OTOGL, AT2B1, ANK3, CA2D1, DPYL2, STXB1, DCTN1, U5S1, GFRA2, GALT1, SEM4D, KIF3C, PLCA, PHB2, NCAM2, GRAK, PURB, IMA3, IMA7, PLD3, FOLH1, FKBP8, STX1A, PSDE, VIAAT, AP1B1, C1QBP, SYT3, HNRH1, SATT, CTND2, SDC4, AP3D1, RGS9, RGS7, CSK22, OX2G, AAKG1, CRYM, PROM1, CNTP1, ENTP2, BCKD, SNG1, NIPS1, NIPS2, SEPT7, AT2A2, PI51C, PI42A, ITB5, GPX4, NPTX2, GNAZ, WDR1, S4A4, MTX2, CNTFR, ZFR, CSN3, HCN2, HCN1, CTBP1, BSN, MPP3, NOE1, CBPD, LGMN, COR1A, CYB, COX1, COX2, COX3, HPRT, ATP6, THY1, H3C, LAMC1, NU1M, NU2M, NU4M, NU5M, ATP8, GFAP, MBP, PRIO, ALDOA, KAPCA, AATM, TBA1B, TBA3, KIT, LDHA, G6PI, MDR1B, ENPP1, HS90A, ENPL, KCC4, NFL, NFM, RASN, PGK2, ITB1, PPBT, NUCL, PGK1, ACE, LRC4B, UBB, UBC, EF1A1, IF4A2, GSTM1, 4F2, H10, LAMP1, HS90B, L1CAM, ITA5, KCC2A, ITB2, ITPR1, TCPA, PFKAL, CNTN1, NCAM1, AT1B1, C1QB, RS16, RL7, AT1B2, PSMD3, MAP1B, GLNA, CADH2, INSR, NTRK2, KCNC1, SPTB1, H12, KPCE, LDHB, CN37, DDX3L, KCNA1, KCNA3, AMPE, ASSY, SPTN1, G3P, LAMP2, ENOA, AP2A1, AP2A2, HXK1, GTR1, PTPRA, COF1, GNAO, FAS, LAMA1, NFH, COX41, BIP, HEXB, VIME, MTAP2, MAG, GNA11, GNAQ, MDR1A, ACES, GBRG2, AP1G1, GBRD, EIF3A, CXA1, GRIA1, GRIA2, TY3H, RS2, GBRA2, RL3, BRAF, KCC2B, NP1L1, NCKP1, SNAB, KIF3A, PABP1, GBB4, KCRU, GNA14, KAP3, SC6A1, S6A11, MP2K1, GTR3, LA, RASK, SYWC, KIF1A, HYES, RAB3D, RAB5C, RAB6A, RAB21, NMDZ1, ODPA, RET, FBRL, KCNJ2, CD81, GPM6A, GPM6B, GNL1, DYN1, DYN2, GRIK2, CAP1, ABCA2, PURA, HD, EAA2, H14, H15, H13, ITAV, SYT1, NSF, RB11B, AINX, MYO1B, NEDD4, ALDH2, GRM8, CAZA2, CAPZB, MP2K4, PFKAM, RL6, RL29, RL5, GLRB, DCE1, DCE2, CBR1, GSTM5, ADT1, INPP, CDK5, SAHH, GDIA, VATA, VATE1, GBRB1, RAB7A, ACADL, VA0D1, ADT2, EAA3, KCNJ4, KPYM, RAB2A, PRS6B, PTN5, NCAN, ABCD3, RAB8A, ATPK, ATP5E, UBP5, ATPB, CTBP2, EAA1, WFS1, FUS, NICA, ACTN4, ASM3B, EF2, OPA1, DOCK4, IRPL1, ARPC4, MYPR, PLPP, ACTB, MDGA2, NEUG, RAC3, IF4A1, MEGF8, RAB5B, RAB10, RAB8B, ARP2, ACTZ, CSN2, ARF3, ARL1, CAH10, RAP2B, STX1B, RAB6B, RL27, ARF4, GABT, 1433G, RS7, PP1A, RS8, SMD1, KCAB2, ABI2, RB11A, EF1A2, RS4X, PP2AB, RL18A, ACTA, AP2S1, RL23A, VISL1, H4, GBRA1, VATB2, RAB1A, RAB3C, RAN, RAP1A, RS24, GBB1, GBB2, RS3, RL8, RS27A, RL40, RAC1, RAB3A, HSP7C, CH60, VAMP2, NOE3, GBRB3, VATL, PP1G, 1433Z, GBRB2, KCNA2, KCAB1, CRNL1, DYL1, ACTG, ACTH, KPCG, PP2BA, PP2AA, PHB1, CSK2B, ACTC, RACK1, ACTS, KAPCB, TBA4A, TBA1A, TBB4B, KPCB, H31, IMB1, PLXA1, PLXA2, PLXA3, DCC, ITPR3, NCHL1, HNRH2, ELAV1, USP9X, IDHG1, LYAG, AT8A1, TCPH, TCPB, TCPD, TCPE, TCPZ, TCPG, TNIK, WNK1, RL36A, ARF1, ARF5, AP2M1, H32, H33, ADCY5, NPTN, RS3A, AT1B3, DPYL1, ZNT3, GRM1, SHPS1, NEO1, M4K4, C1QA, TBB5, PDE4D, PDE1B, NMDE2, SC23A, TERA, C1QC, CTNB1, PLAK, EPHA4, MARK3, ATPA, CHLE, KCND1, KCRB, NF1, CDK18, RAC2, MARK2, PGBM, PTPRG, PYC, KCMA1, PADI2, INF2, TRIO, MDGA1, CTP5A, ITB8, PSA, GRM2, PTCD3, PHAR1, LRFN1, SPP2B, HP1B3, NLRX1, PRC2C, TM38A, VGLU1, BIG3, PLXD1, AGAP2, AAK1, TEN4, CAMKV, DOP2, RMD3, SMU1, MCCB, GPD1L, LIGO2, SRBS2, CDKL5, K22O, VPS51, GRM5, CBAR2, SHAN3, UN13A, SE6L2, KCTD8, KCD16, LRC8B, VP13A, C2C4C, S2551, MRS2, DIRA2, CYFP2, TM1L2, RHG44, MYO1D, RABL6, DJC11, UIMC1, ICAM5, FLOT2, HNRPD, PTPRN, CSK21, KHDR1, IGF1R, CLD11, SPB6, ARHG2, VDAC2, VDAC3, VDAC1, ABCB7, ASTN1, P3C2A, CAC1E, LAMB2, CTNA2, SC6A3, CNTN2, PGCB, NEP, KCNA4, CD166, 5NTD, GSLG1, EWS, AP180, FSCN1, GDIB, GRIK5, GRID1, DDX5, ITIH3, IL1AP, CD47, KINH, KIF3B, LASP1, MYH10, MOG, NPM, PCBP2, CSPG2, DDX3Y, DLG4, RHOC, DAG1, DDX3X, SYPH, TICN1, NDUA4, NPTX1, NUP62, OMGP, HECAM, AOFA, ARP3B, SURF4, SYN2, CP3AD, H2B1H, GLPK, SDC3, GPDM, H2A2C, H2B2B, GRM7, GRM4, CLH1, K1549, GIT1, PKP4, PPR29, CNTN4, NLGN2, SV2C, THS7A, CE170, UBP7, BRNP2, SCMC3, LIGO3, DGKB, RPRD2, DPP10, S23IP, PPRC1, 2ABA, TNPO3, SIK3, U520, S39AA, TTYH3, XPO1, SPCS, KCRS, CSKI1, NRX3A, BCR, SARM1, PRRT3, TEFF1, RAB35, CA2D2, KCC2D, AT1A3, AT1A2, GNAS1, SDK2, WDFY3, NTRK3, RAD9B, DGLA, KCD12, MTMR5, UBE2O, CAND1, UBP34, RS9, 2ABB, H2B1C, TLN2, CSPG5, 2AAA, NP1L4, MTCH2, OPALI, CYFP1, TBB2A, HUWE1, IGS21, ROBO2, ACTN1, IGSF1, TR143, TPPP, OTUB1, KPBB, PP6R1, MAP6, ELP1, RRAGD, MRCKB, GABR2, CSMD3, EPT1, VAT1L, LRRC7, CAPS1, CYLD, AGRL1, AGRL3, CLAP1, AUXI, DAAM2, MADD, MFN2, NU214, UBE3C, PLXA4, FBX2, KCMF1, CBPM, GSTM7, AGFG2, LRC8A, HPLN4, VAC14, UBP2L, C2C2L, LRRT4, BDH, MK15, CNKR2, TENA, ASTN2, NEGR1, RAP2A, THEM6, SLIK5, SLIK4, SLIK3, SLIK2, NFASC, NRCAM, RHG32, SRGP3, EFTU, VGLU3, ERLN2, SV2B, MIRO1, EFR3A, LRRT2, U2AF4, ENPP6, SYAC, FLRT3, CBLN2, LRTM2, HPCL4, COR2B, S2512, ATLA1, NU107, RB39B, RB39A, ZN526, ANS1B, DLGP2, AHSA1, IPO5, NCEH1, LSAMP, CADM2, NOE2, ODP2, RBGPR, ECHA, SPA2L, SYNC, RL24, DAAM1, DMXL2, RLGPB, CLAP2, VMAT2, ARF2, NDRG4, ENPP4, HSDL1, RAP2C, GEPH, VATH, PMGT2, TTC12, AOFB, LRFN5, PIGT, CTL2, TENR, NLGN3, LRRT3, DYN3, LRC4C, ARHGA, SYFA, SI1L1, LCAP, EXOG, CERS6, SEP11, IKZF4, GP158, CWC22, VPS52, SCAI, ANK2, PDE10, PGM2L, SHFL, MIC60, WDR37, ABI1, SYNPO, T132C, GLT13, NED4L, RPB2, TCRG1, GNAL, H2B1K, H2B1P, H2A1F, H2A1H, H2A1K, OGT1, SYNJ1, SEPT8, MBOA7, PGP, NGEF, PYGB, COPA, MARK4, DOCK3, PLXB1, TXTP, AGRL2, TRHDE, R4RL1, RTN1, HS12A, K319L, DNM1L, AGRG1, PACS1, ABCF3, SDHA, HACD3, AGFG1, PAF1, IPO11, CCM2, MATR3, ATAT, LRRT1, LGI3, RPTOR, COL12, NAC2, THIL, EIF3L, MARE2, HNRPL, K0513, IQEC1, CACB4, SCPDL, BPHL, SNG3, EIF3C, H2AJ, DC1L1, S35A3, AP3M2, MUC18, UBQL1, PSPC1, NUP58, IGSF8, EXOC1, CACB1, CADM4, NUP85, SNP47, ACTY, WASF1, AMPB, MICU1, PSMD2, AT1A1, CDIPT, GD1L1, CC50A, HNRPU, REM2, S25A3, MARK1, CSPG4, SORC3, IPO4, SFPQ, BACH, S12A5, RAB14, SFXN3, ACLY, NDUS1, ITM2C, RMXL1, MIC25, ATPG, DDX1, MLP3A, UBAP2, ACSL6, NDUS2, ERLN1, DLG2, PI42C, IPO9, NDUV1, GRHPR, SRGP2, SRGP1, RAB4B, LRP1, WDR7, BRNP1, SYDC, TBB6, PDK3, TSN2, PDE2A, RPAB3, CSMD1, KCC2G, 2ABD, ATAD3, SFXN5, MYO5A, G37L1, RAP1B, SFXN1, NLGN1, NONO, RRAGC, TIP, MLF2, GAK, CDS2, NDUAA, ETFA, TNPO2, PTPRT, DNJA3, T121B, SF3B1, RIMS1, CNTP4, NTRI, PRP8, COX6C, MGST3, CNTP2, 6PGL, QCR8, NDUB4, RAB5A, GLRX3, AT5F1, S2546, MLP3B, 1433B, RL14, M2OM, UCRI, MIC19, PRPS2, NRX1A, MICU3, ARPC2, TBB2B, ROA0, CENPV, RL11, ILF2, TECR, RN181, BIEA, QCR1, OLA1, RL15, AL1B1, TOM70, MPC2, ODPB, MMS19, MGRN1, HNRPM, SCOT1, DYL2, RM28, RAB1B, LIGO1, RUFY3, MEII1, ATAD1, CUL5, GBRA4, TBB4A, GHC1, IDH3A, PRPS1, U2AF1, RL4, PSD12, SNAA, ATPO, BTBDH, QCR2, ALG2, AP2B1, RPN2, SUSD2, NDUA9, NDUS7, 6PGD, EIF3F, NDUS3, RAB13, XPO7, IPO7, NBEA, SORC2, VPS35, RPGF4, TBB3, XPO2, RTN3, LRBA, SPN90, TRIM2, DYHC1, LRP1B, LGI1, PRAF2, SV2A, SCAM5, NECT1, HYOU1, EXTL1, SORC1, DCLK1, MTOR, MINK1, ZN207, AP3B2, RHOA, HPLN1, FAK2, NAGAB, COPG2, KI21A, SHRM3, PLEC, DREB, S2513, EHD3, PLXB3, ADDA, DNJA2, GRM3, PCLO, SIA7A, ARP10, DCTN5, PLXC1, COPG1, GPC1, UBQL2, FBX6, SRR, AT2B2, CELR2, DEST, ARC1A, KAD1, GBRG1, GUAD, CBLN1, DGKE, VAS1, ADA22, ADA23, PEPL, CAD13, TEN1, TEN2, CUL1, ATRN, GLPK2, PDC6I, PFKAP, PYGM, SUCA, RBMX, GABR1, GSK3B, FPRP, E41L3, BUB3, CARM1, PSD13, CP46A, APC7, NCDN, ITB6, KCND2, NU160, HNRDL, SAE2, VATC1, VPP1, ARI1, CA2D3, SEPT3, AP3B1, STK39, DPP6, E41L1, SUCB1, SEPT5, GRIA4, GRIA3, HOME1
Species: Mus musculus
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