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. 2020 Oct 1;19:146. doi: 10.1186/s12943-020-01262-x

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© The Author(s) 2020

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 2 — Regulation of metabolic enzymes by ubiquitination and deubiquitination in cancer metabolism. Glycolysis is upregulated to provide more glycolytic intermediates for biosynthesis of macromolecules. Glutamine uptake is enhanced to maintain mitochondrial ATP production. Fatty acids synthesis is increased for membrane biosynthesis. Metabolic enzymes involved in the glucose, fatty acid and amino acid metabolic pathways are under the regulation of ubiquitination and deubiquitination to control cancer metabolism. The ubiquitin ligases and deubiquitinating enzymes in red font positively regulate the activity or expression level of substrate proteins. The ubiquitin ligases and deubiquitinating enzymes in blue font negatively regulate the activity or expression level of substrate proteins. ACC, Acetyl-coenzyme A carboxylase; ACLY, ATP citrate lyase; ACO1/2, Aconitate hydratase 1/2; ACS, Acyl-CoA synthetase; ADI, Arginine deiminase; ALDOA, Fructose-bisphosphate aldolase A; ARG, Arginase; ASCT2, Neutral amino acid transporter B; ASL, Argininosuccinate lyase; ASS, Argininosuccinate synthase; CPT1, Carnitine O-palmitoyltransferase 1; CS, Citrate synthase; ENO 1, Enolase 1; FASN, Fatty acid synthase; FH, Fumarate hydratase; G6PD, Glucose-6-phosphate dehydrogenase; GAPDH, Glyceraldehyde-3-phosphate dehydrogenase; GLS1, Glutaminase 1; GLUD1, Glutamate dehydrogenase 1; GLUT1, Glucose transporter type 1; GOT, Aspartate aminotransferase; HK1, Hexokinase 1; HMGCR, 3-hydroxy-3-methylglutaryl-coenzyme A reductase; IDH1/2, Isocitrate dehydrogenase1/2; LDHA, L-lactate dehydrogenase A chain; MDH, Malate dehydrogenase; ME, NADP-dependent malic enzyme; PDH, Pyruvate dehydrogenase; PDK, Pyruvate dehydrogenase kinase; PFK, Phosphofructokinase; PFKFB3, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3; PFKL, PFK liver type; PFKP, PFK1 platelet isoform; PGAM5, Phosphoglycerate mutase 5; PGK1, Phosphoglycerate kinase 1; PHGDH, D-3-phosphoglycerate dehydrogenase; PKM2, Pyruvate kinase M2; PRODH, Proline dehydrogenase; PSAT1, Phosphoserine aminotransferase 1; PSPH, Phosphoserine phosphatase; PYCR, Pyrroline-5-carboxylate reductase; SDH, Succinate dehydrogenase; SHMT1, Serine hydroxymethyltransferase 1; SQLE, Squalene epoxidase; TCA, Tricarboxylic acid; α-KGDH, α-ketoglutarate dehydrogenase