{"database":"JPOST Repository","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Xlsx":["https://storage.jpostdb.org/JPST003484/files/Searching%20Results.xlsx"],"Other":["https://storage.jpostdb.org/JPST003484/files/Phosphoproteomics%20for%20RBE,%20SSP25%20and%20AG120%20treated%20RBE.7z","https://storage.jpostdb.org/JPST003484/files/Peak%20list_AG120_DMSO_RBE.7z","https://storage.jpostdb.org/JPST003484/files/0-0.5mM%20CoCl2%20treated%20H293T.7z","https://storage.jpostdb.org/JPST003484/files/AG120_DMSO_RBE.7z","https://storage.jpostdb.org/JPST003484/files/Peak%20list_RBE_SSP25.7z","https://storage.jpostdb.org/JPST003484/files/Peak%20list_0-50mM%20D2HG%20treated%20H293T.7z","https://storage.jpostdb.org/JPST003484/files/RBE_SSP25.7z","https://storage.jpostdb.org/JPST003484/files/Peak%20list_0-50mM%20L2HG%20treated%20H293T.7z","https://storage.jpostdb.org/JPST003484/files/0-50mM%20D2HG%20treated%20H293T.7z","https://storage.jpostdb.org/JPST003484/files/Phosphoproteomics%20for%20H293T%20cells%20treated%20with%20or%20without%200,2mM%20CoCl2.7z","https://storage.jpostdb.org/JPST003484/files/Peak%20list_0-72h%20LowO2%20cultured%20H293T.7z","https://storage.jpostdb.org/JPST003484/files/Peak%20list_Phosphoproteomics%20for%20H293T%20cells%20treated%20with%20or%20without%200.2mM%20CoCl2.7z","https://storage.jpostdb.org/JPST003484/files/0-50mM%20L2HG%20treated%20H293T.7z","https://storage.jpostdb.org/JPST003484/files/0-72h%20LowO2%20cultured%20H293T.7z","https://storage.jpostdb.org/JPST003484/files/Isotopic%20d4-2HG%20treated%20H293T.7z","https://storage.jpostdb.org/JPST003484/files/Peak%20list_0-0.5mM%20CoCl2%20treated%20H293T.7z","https://storage.jpostdb.org/JPST003484/files/Peak%20list_Isotopic%20d4-2HG%20treated%20H293T.7z","https://storage.jpostdb.org/JPST003484/files/Peak%20list_Phosphoproteomics%20for%20RBE,%20SSP25%20and%20AG120%20treated%20RBE.7z"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"scores":null,"additional":{"omics_type":["Proteomics"],"submitter":["W. Andy Tao"],"species":["Homo Sapiens (human)"],"full_dataset_link":["https://repository.jpostdb.org/entry/JPST003484"],"submitter_affiliation":["Purdue University"],"sample_protocol":[""],"repository":["jPOST"],"data_protocol":[""],"name_synonyms":["Protein Gene Products, Gene Products, Proteins, Gene Proteins, Gene, protein, native protein, protein aggregate, protein-containing complex, Protein., protein complex, Protein"],"description_synonyms":["sodium salt, DNA Oxidative, MGC130048, Post Translational Amino Acid Modification, isocitrate dehydrogenase, DmelCG8566, posttranslational modification, DmelCG4527, ion, single-organism developmental process, 9A2, postnatal development, FBgn0038922, A4, Nitrative Stress, growth and development, mNADP-IDH, Visible Light, DmKlp53D, Etk4, Tumor, 2-hydroxyglutarate, Protein Processing, Damage, phosphorylation, Oxygen Deficiencies, SMAK, 1H-imidazoleacetic acid, Oxidative DNA, Roles, Oxidative, Nitro-Oxidative Stress, Concepts, Impacts, Nitro-Oxidative Stresses, Kinase, Environmental Impacts, Oxidative Injury, DNA Damage, IKKg, KEY, Key, PICD, Post-Translational Protein, treatment, gamma sarcoglycan, Cytosolic NADP-isocitrate dehydrogenase, Oxidative Injuries, posttranslational amino acid modification, thymus nucleic acid, ostium, protein modification, Post-Translational, Oxidative Cleavage, Oncogeneses, D2HGA2, se20-9, Oxidative DNA Damages, Posttranslational Protein Processing, Anti-oxidative, NADP(+)-specific ICDH, Oxygen, Environmental Impact, IMAC, TNFSF14, Oxidative Stress Injuries, Oxidative Stresses, malignant neoplasm, signaling process, IDPC, Role Concepts, disease management, Therapies, gamma-sarcoglycan, process resulting in protein modification, Double-Stranded DNA, Malignancies, deoxyribonucleic acids, imac, DNAn, ATP Phosphotransferases, cellular protein modification process, IDPM, Reference Standard, ostia, ATP, single organism signaling, Tumors, Therapy, Post-Translational Modification, Standard Preparation, Standard Preparations, AW411554, Standardization, Radiation, Metal, IDH, Idh, UNQ391/PRO726, TSC-1, (D)-isomer, Modifications, SG-gamma, Up-Regulation (Physiology), IDP, l(3)L3852, Light, Double-Stranded, AV021402, foramina, KIF1B, IDCD, (Deoxyribonucleotide)n+m, DmIKKgamma, Post Translational Modifications, Role Concept, LIGHT, Benign, Ionen, SYN, dIKK, Oxidative and Nitrosative Stress, idh, bA16H23.1, Kenny, Role, sarcoglycan, DNA Oxidative Damages, CG8566, desoxyribose nucleic acid, region, CG4527, Visible Radiations, imidazole-4-acetic acid hydrochloride, Transphosphorylases, (DL)-isomer, alpha-hydroxyglutarate, Visible Radiation, PTM, HVEML, growth pattern, CT22171, Standard, Upregulation, non-developmental growth, Processing, disodium salt, IKK-gamma, Hypoxemia, Benign Neoplasms, gamma (35kDa dystrophin-associated glycoprotein), Treatments, Oxalosuccinate decarboxylase, Malignant Neoplasms, Nitro-Oxidative, 1.1.1.42, DmCG8566, DMDA, DmelCG16910, SCYA26, Amino Acid Modification, Oncogenesis, MRCK, 35kD dystrophin-associated glycoprotein, post-translational modification, DmelCG6439, ds DNA, Slik1, Oxidative Stress Injury, Posttranslational Modifications, DNA, Anoxemia, Posttranslational Modification, D-2-hydroxyglutarate, Oxidative Damage, Plkk/Slik, Proto-oncogene c-Fyn, Oxidative Stress, biological signaling, Dunc104, Tumorigeneses, criteria, SGCG_HUMAN, Post-Translational Protein Modifications, DNS, (Deoxyribonucleotide)n, Peptidomics, Antioxidative, Neoplasms, Deficiencies, Benign Neoplasm, Antioxidative Stress, SLK, Slk, Gene, PK428, guidelines, Malignant, dIKK-gamma, TYPE, Deoxyribonucleic acids, Posttranslational, Stresses, Ly113, DAGA4, Oxygen Deficiency, Oxidative Nitrative, Deoxyribonucleic Acid, Stress Injury, DmIKK-gamma, 35DAG, Post Translational Modification, Gene Products, Oxidative Cleavages, slk, Post-Translational Modifications, dmIKKgamma, IKK[[gamma]], MAM, gamma-SG, LOSK, Hypoxia, SCG3, HEL-216, Phosphotransferase, Oxidative Damages, Post Translational, Modification, IDHM, Injury, dPlkk, Malignancy, Receptor Up-Regulation, iones, STK2, Up Regulation, Stk2, imidazolyl-4-acetic acid, Double Stranded, Treatments., Deoxyribonucleic acid, posttranslational protein modification, Transphosphorylase, Visible, ions, DmelCG7176, Protein Modifications, Post-Translational Amino Acid Modification, Neoplasias, 2.7.10.2, IDH-NADP, Reference, IDH2, IKK, MIP-4a, Anti oxidative Stress, Posttranslational Amino Acid Modification, Oxidative DNA Damage, Antioxidative Stresses, Posttranslational Protein, site, (L)-isomer, (Deoxyribonucleotide)m, TR2, Preparation, MRCKA, Slik, Cancer, Idh-NADP, foramen, 2-hydroxyglutaric acid, Malignant Neoplasm, 35 kDa dystrophin-associated glycoprotein, dPlkk/Slik, ICD-M, DNAn+1, imidazole-4-acetic acid, Proteins, Phosphorylations, Post-Translational Protein Modification, Anti-oxidative Stresses, Tumorigenesis, CD258, Cell, Phosphotransferases, SGCG, LGMD2C, Concept, Impact, development, Environmental, IKKgamma, Anoxia, Oxidative Nitrative Stress, mKIAA0204, MT, Unc104, Oxidative Nitrative Stresses, Protein, HEL-S-26, Plkk1, Neoplasm, ds-DNA, Proto-oncogene Syn, mSLK, Protein Modification, Radiations, p59-Fyn, p59-FYN, primary cancer, Anti-oxidative Stress, DMDA1, DNA Oxidative Damage, CG7176, Dmikkgamma, Kinases, HVEM-L, Post Translational Protein Processing, Carcinogeneses, postnatal growth, Photoradiation, DPlkk1, MIP-4alpha, Klp53D, Cancers, Cleavage, CG16910, malignant tumor, Unc-104, signalling, post-translational amino acid modification, PLKK1, LTg, Protein Gene Products, Gene Proteins, Preparations, Post Translational Protein Modification, Deficiency, Photoradiations, signalling process, Ion, Therapeutic, opening, SCARMD2, Stress, Standards, Post-Translational Protein Processing, Environments, Desoxyribonukleinsaeure, Src-like kinase, Treatment, Nitro Oxidative Stress, growth, Neoplasia"],"additional_accession":[]},"is_claimable":false,"name":"Discovery of Chiral D2HG and L2HG mediated Protein O-2-Hydroxyglutarylation","description":"Oncometabolites including D-2-hydroxyglutarate (D2HG) and L2HG have come under the spotlight due to their roles in promoting tumorigenesis. These oncometabolites dysregulate growth-signalling pathways by noncovalently interacting with key regulators. However, it is unclear whether D/L 2HG influence cellular functions through covalent protein modification. Here we discovered a novel type of posttranslational modification by a novel unbiased immobilized metal ion affinity chromatographic (IMAC) based strategy and further confirmed it as the O-2-Hydroxyglutarylation. We found D2HG modification undergo upregulation upon D2HG treatment or in IDH mutant cells, while L2HG modification upregulate upon L2HG treatment or in hypoxia environment. By differential proteomics, we distinguished the enantiomer D2HG and L2HG modifications and constructed D2HG and L2HG modification datasets, and some of them were validated by isotopic metabolic flux approach. Quantitative proteomics identified O-2-Hydroxyglutarylation sites in multiple functional proteins, including DNA replicators and responders to oxidative stress. Two kinase, MRCKA bearing D2HG modification at site S794 and SLK bearing L2HG at S719 have been identified and confirmed by synthetic peptide standards. Phosphoproteomics revealed that the phosphorylation level of MRCKA and SLK's substrate downregulated in D2HG and L2HG accumulated cells respectively, suggesting a inhibitory effect of 2HG modification on kinase. The discovery of O-2-Hydroxyglutarylation shed light on the intricate relationship between cancer progression and the oncometabolites D/L-2HG, opening new pathways for the development of more effective cancer treatments.","dates":{"publication":"Sat Jan 25 00:00:00 GMT 2025"},"accession":"PXD059758","cross_references":{"TAXONOMY":["9606"]}}