Citrate synthase desuccinylation by SIRT5 promotes colon cancer cell proliferation and migration
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Mengmeng Ren
, Xin Yang , Juntao Bie , Zhe Wang , Minghui Liu , Yutong Li , Genze Shao und Jianyuan Luo
Abstract
Citrate synthase (CS), the rate-limiting enzyme in the tricarboxylic acid (TCA) cycle catalyzes the first step of the cycle, namely, the condensation of oxaloacetate and acetyl-CoA to produce citrate. The expression and enzymatic activity of CS are altered in cancers, but posttranslational modification (PTM) of CS and its regulation in tumorigenesis remain largely obscure. SIRT5 belongs to the nicotinamide adenine dinucleotide (NAD)+-dependent deacetylase sirtuin family and plays vital roles in multiple biological processes via modulating various substrates. Here, we show that SIRT5 interacts with CS and that SIRT5 desuccinylates CS at the evolutionarily conserved residues K393 and K395. Moreover, hypersuccinylation of CS at K393 and K395 dramatically reduces its enzymatic activity and suppresses colon cancer cell proliferation and migration. These results provide experimental evidence in support of a potential therapeutic approach for colon cancer.
Funding source: National Natural Science Foundation of China
Award Identifier / Grant number: 81874147, 81671389
Acknowledgments
We thank the core facility at Peking University Health Science Center for mass-spectrometry analysis. This study was supported by the National Natural Science Foundation of China, No. 81874147, 81671389.
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© 2020 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Reviews
- Redefining proteostasis transcription factors in organismal stress responses, development, metabolism, and health
- Proteostasis in thermogenesis and obesity
- Research Articles/Short Communications
- Protein Structure and Function
- Citrate synthase desuccinylation by SIRT5 promotes colon cancer cell proliferation and migration
- Membranes, Lipids, Glycobiology
- Core 1 O-N-acetylgalactosamine (O-GalNAc) glycosylation in the human cell nucleus
- Cell Biology and Signaling
- LncRNA ELFN1-AS1 promotes esophageal cancer progression by up-regulating GFPT1 via sponging miR-183-3p
- Vemurafenib downmodulates aggressiveness mediators of colorectal cancer (CRC): Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP), Protein Tyrosine Phosphatase 1B (PTP1B) and Transforming Growth Factor β (TGFβ)
- Osteopontin enhances the migration of lung fibroblasts via upregulation of interleukin-6 through the extracellular signal-regulated kinase (ERK) pathway
- A role of heparan sulphate proteoglycan in the cellular uptake of lipocalins ß-lactoglobulin and allergen Fel d 4
- A progesterone receptor membrane component 1 antagonist induces large vesicles independent of progesterone receptor membrane component 1 expression
Artikel in diesem Heft
- Frontmatter
- Reviews
- Redefining proteostasis transcription factors in organismal stress responses, development, metabolism, and health
- Proteostasis in thermogenesis and obesity
- Research Articles/Short Communications
- Protein Structure and Function
- Citrate synthase desuccinylation by SIRT5 promotes colon cancer cell proliferation and migration
- Membranes, Lipids, Glycobiology
- Core 1 O-N-acetylgalactosamine (O-GalNAc) glycosylation in the human cell nucleus
- Cell Biology and Signaling
- LncRNA ELFN1-AS1 promotes esophageal cancer progression by up-regulating GFPT1 via sponging miR-183-3p
- Vemurafenib downmodulates aggressiveness mediators of colorectal cancer (CRC): Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP), Protein Tyrosine Phosphatase 1B (PTP1B) and Transforming Growth Factor β (TGFβ)
- Osteopontin enhances the migration of lung fibroblasts via upregulation of interleukin-6 through the extracellular signal-regulated kinase (ERK) pathway
- A role of heparan sulphate proteoglycan in the cellular uptake of lipocalins ß-lactoglobulin and allergen Fel d 4
- A progesterone receptor membrane component 1 antagonist induces large vesicles independent of progesterone receptor membrane component 1 expression