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Lin CH, Liao CC, Wang SY, Peng CY, Yeh YC, Chen MY, Chou TY. Comparative O-GlcNAc Proteomic Analysis Reveals a Role of O-GlcNAcylated SAM68 in Lung Cancer Aggressiveness. Cancers 2022 14(1) 35008409
Abstract:
O-GlcNAcylation is a reversible and dynamic post-translational protein modification catalyzed by O-GlcNAc transferase (OGT). Despite the reported association of O-GlcNAcylation with cancer metastasis, the O-GlcNAc proteome profile for cancer aggressiveness remains largely uncharacterized. Here, we report our comparative O-GlcNAc proteome profiling of two differentially invasive lung adenocarcinoma cell lines, which identified 158 down-regulated and 106 up-regulated candidates in highly invasive cells. Among these differential proteins, a nuclear RNA-binding protein, SAM68 (SRC associated in mitosis of 68 kDa), was further investigated. Results showed that SAM68 is O-GlcNAcylated and may interact with OGT in the nucleus. Eleven O-GlcNAcylation sites were identified, and data from mutant analysis suggested that multiple serine residues in the N-terminal region are important for O-GlcNAcylation and the function of SAM68 in modulating cancer cell migration and invasion. Analysis of clinical specimens found that high SAM68 expression was associated with late cancer stages, and patients with high-OGT/high-SAM68 expression in their tumors had poorer overall survival compared to those with low-OGT/low-SAM68 expression. Our study revealed an invasiveness-associated O-GlcNAc proteome profile and connected O-GlcNAcylated SAM68 to lung cancer aggressiveness.
O-GlcNAc proteins:
A0A024R7P5, A0A024R9E2, A0A087WWU8, A0A0A0MTS7, SHOT1, A8K3C3, A8K9J7, B7Z2Z8, B7Z596, D3DS63, E7ETM0, E7EVA0, F8VR77, H0YN18, H3BPE1, K7ERG4, PSD12, DFFA, PLOD2, PSDE, BIN1, TCRG1, ML12B, HGS, HNRDL, RPAC1, P4HA2, HNRPR, PLRG1, ZN207, BUB3, ACTN4, KDM1A, PLOD3, CPNE3, FLNB, NU155, GLRX3, MTA2, SC31A, UBE4B, TFR1, ANXA1, HSPB1, ITB1, DCUP, GELS, ENOA, NPM, TPM3, LDHB, ANXA2, TBB5, HNRPC, TPM2, ANXA6, 4F2, VIME, ANXA5, RSSA, ENOG, TPM1, PARP1, UBB, UBC, CH60, ACADM, G6PD, PCNA, KCRB, KCRU, ACTN1, XRCC6, EF2, KAP2, SYDC, AMPN, EZRI, NAGAB, HMGA1, ML12A, AOC1, ICAL, VATB2, FLNA, OSBP1, UBA1, GCSH, PSA1, PSA3, SYVC, TPP2, CLIP1, HNRH3, KINH, HSP74, RADI, MYH9, MYH10, ACTN2, ADDA, FUS, MYH11, RL4, ODO2, VATA, CAP2, GARS, MSH2, PRS6B, UBP5, RS9, MAP1B, IQGA1, KC1A, NASP, FAS, SYAC, NU153, HDGF, ACLY, SYYC, RD23A, PSMD4, TERA, EIF3B, IF6, PSA6, RS3A, HNRPK, 1433G, PP1B, PRS8, RL7A, PP2AB, RS6, RL10A, RS27A, RL40, 2ABA, TPM4, EF1A1, GTF2I, RAE1L, HNRPU, SPTB2, EWS, PLCB3, FKBP4, IF4G1, SSBP, 1433F, PUR1, PRDX1, KHDR1, ACTN3, PP2BA, ILF2, ACACA, CBX3, G3BP1, EIF3I, DC1I2, ROCK1, HDAC1, CUL1, NACA, SPTN1, SMC1A, GANAB, PSME4, SYK, PLEC, PP1R7, SC23A, SC23B, TSN, CIP4, MARE1, DDB1, CART, RBBP7, ACTBL, ST1C3, P4R3A, Q6IPH7, C2D1A, POTEE, SND1, CYFP1, MON2, MYH14, CAND1, ABCA7, LRC47, THMS1, CPSF7, GT251, SERB1, ABCF1, Q8TDJ5, Q8WWH9, AGRV1, TCPW, TFG, STAM1, SNR40, VPS35, SIN3A, NIBA2, PSB7, TSNAX, DHRS6, RBM4, XRN2, SPTN4, SLK, MYG1, XPP1, UGGG1, CPSF2, NAGK, NUDT5, PRP19, UBQL1, PACN2, SNX6, NCKP1, HYOU1, LSM4, SNX5, S23IP, V9HVZ7, V9HW77
Species: Homo sapiens
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Wang J, Dou B, Zheng L, Cao W, Zeng X, Wen Y, Ma J, Li X. Synthesis of Na(2)S(2)O(4) mediated cleavable affinity tag for labeling of O-GlcNAc modified proteins via azide-alkyne cycloaddition. Bioorganic & medicinal chemistry letters 2021 48 34229054
Abstract:
A facile and convergent procedure for the synthesis of azobenzene-based probe was reported, which could selectively release interested proteins conducted with sodium dithionite. Besides, the cleavage efficiency is closely associated with the structural features, in which an ortho-hydroxyl substituent is necessary for reactivity. In addition, the azobenzene tag applied in the Ac4GlcNAz-labled proteins demonstrated high efficiency and selectivity in comparison with Biotin-PEG4-Alkyne, which provides a useful platform for enrichment of any desired bioorthogonal proteomics.
O-GlcNAc proteins:
PGP, EIFCL, KIF2A, PDLI1, BACH, DFFA, CLIC1, EIF3F, IF2B3, RTCA, PSDE, PPP6, RPC1, PSA7, HNRDL, SC16A, RPAC1, NKRF, EIF3H, PAPS1, SNUT1, ARK72, MYO1B, IDH3B, SAHH2, PLIN3, IMA7, UGDH, CTND1, SNX2, BRD4, WDR1, TBCA, FLNB, PR40A, MPPB, NDUS3, ECI2, CSDE1, U520, WDHD1, EIF3G, PSD10, IDHC, GLRX3, RL1D1, CIAO1, PLPHP, ERLN2, GLSK, SC31A, UBR5, ELP1, VAPB, 6PGL, AGM1, AHSA1, PSMG1, SGPL1, AP2A1, STAU1, TTC4, BPNT1, MBD3, TOM40, ACL6A, GSHR, PNPH, CYTB, KITH, P53, TPM3, PROF1, FUMH, ODPA, CY1, SRP19, DLDH, RU2A, UCHL1, ALDOC, THIO, KAP0, ESTD, ODPB, PYGB, ACADM, G6PD, ADHX, CDK4, HARS1, PEPD, P4HA1, ETFA, MIF, AK1A1, CCNB1, GLNA, DESP, FER, UBF1, PRS6A, RL35A, NELFE, RCC1, E2AK2, SPEE, ANXA7, RAB6A, PSB1, IMDH1, GSTM3, VATB2, FLNA, ACOHC, SDHB, PIMT, FBRL, NDKB, ADRO, TCEA1, TBG1, MAOM, IF4B, THTM, RS12, BRD2, DNJB1, PSA1, PSA2, PSA4, STOM, PYR1, PSB4, PSB6, NDUS1, DPOD1, AMPL, ERP29, PRDX3, ECHM, PEBP1, PDIA3, HMOX2, PURA2, PUR8, AL1B1, RPB2, GDIA, TIA1, QCR1, HNRH3, STIP1, PRDX2, P5CR1, DUT, PROF2, SPB6, RADI, T2FA, MYH9, MYH10, FUS, PRS7, MP2K2, HEM6, GNL1, ODO2, SRP14, TALDO, ETFB, VATA, IF4A3, TXLNA, BUD31, CSK, THIM, LIS1, NAMPT, PRS6B, RECQ1, NOP2, CRKL, NSF, CAPZB, COPD, IDHP, AL9A1, RL34, FAS, SYCC, PSB3, IDH3A, SERPH, ANX11, FXR1, FXR2, SMCA4, GALK1, ROA3, HNRPM, IMA5, GDIR1, HNRPF, KIF11, THOP1, CAZA1, BIEA, MAP11, SUCA, SC24C, DRG2, ECHB, DSRAD, HNRH2, IF6, CORO7, ARPC4, CD81, SC61B, MYL6, PSA6, CDC42, SRP54, UB2D3, UBC12, ARP3, RL37A, COPZ1, NTF2, 1433G, PP1A, PP1B,