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Post-Mortem Tissue Analyses in a Patient with Succinic Semialdehyde Dehydrogenase Deficiency (SSADHD)

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Abbreviations NSCLC: Non-small cell lung cancer OXPHOS: Oxidative phosphorylation TME: Tumor microenvironment HIF-1: Hypoxia-inducible factor 1-alpha HK2: Hexokinase 2 PKM2: Pyruvate kinase M2 LDHA: Lactate dehydrogenase A GLS1: Glutaminase ASCT2: Amino acid transporter ASCT2 FASN: Fatty acid synthase SREBP1: Sterol regulatory element-binding protein 1 CAFs: Cancer-associated fibroblasts KRAS: Kirsten rat sarcoma viral oncogene homolog EGFR: Epidermal growth factor receptor TP53: Tumor protein p53 LKB1: Liver kinase B1 KEAP1: Kelch-like ECH-associated protein 1 PI3K-AKT-mTOR: Phosphatidylinositol 3-kinase-AKT-mechanistic target of rapamycin pathway 2-DG: 2-deoxyglucose ACC: Acetyl-CoA carboxylase LAT1: Amino acid transporter LAT1 PHGDH: Phosphoglycerate dehydrogenase FDG-PET: Fluorodeoxyglucose positron emission tomography MRI: Magnetic resonance imaging NAD+: Nicotinamide adenine dinucleotide GPX4: Glutathione peroxidase 4 NRF2: Nuclear factor erythroid 2-related factor 2 PUFA: Polyunsaturated fatty acids MUFA: Monounsaturated fatty acids ROS: Reactive oxygen species TCA: Tricarboxylic acid cycle FAO: Fatty acid oxidation SHMT: Serine hydroxymethyltransferase SAM: S-adenosylmethionine AMPK: AMP-activated protein kinase mTOR: Mechanistic target of rapamycin EMT: Epithelial-mesenchymal transition Treg: Regulatory T cell MDSC: Myeloid-derived suppressor cell TAM: Tumor-associated macrophage PARP: Poly(ADP-ribose) polymerase CRISPR: Clustered regularly interspaced short palindromic repeats CEST: Chemical exchange saturation transfer NAMPT: Nicotinamide phosphoribosyltransferase DCA: Dichloroacetate MCT: Monocarboxylate transporter SCD1: Stearoyl-CoA desaturase 1 ACLY: ATP citrate lyase HMGCR: HMG-CoA reductase DLR: LDL receptor PFKFB3: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 VEGF: Vascular endothelial growth factor PDK1: Pyruvate dehydrogenase kinase 1 SRE: Sterol regulatory element CAIX: Carbonic anhydrase IX Glut-1: Glucose transporter 1 References Alduais Yaser, Zhang Haijun, Fan Fan, Chen Jing, Chen Baoan

Here, we show that the deubiquitylase (DUB) OTUD5 is cooperatively modified by TRIP12 and UBR5, resulting in conjugation of K29/K48 branched ubiquitin chains and accelerated proteasomal degradation