ArticleThe Biochemical journal2014
Identification of protein succination as a novel modification of tubulin.
Article in The Biochemical journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 48 citations in OpenAlex.
- Itaconation and Succination as Metabolite-Derived Cysteine Modifications in Inflammatory Signalling: Biochemical Mechanisms, Chemoproteomic Mapping, and Therapeutic Opportunities.Cell biochemistry and biophysics · 2026Review
- Dimethyl fumarate as a versatile therapeutic agent: molecular mechanisms and potential clinical applications.Molecular biology reports · 2026Review
- Identification of Mitochondrial and Succinylation Modification-Related Gene Signature in Ischemic Stroke.Molecular neurobiology · 2025Article
- A Covalent and Modulable Inhibitor of the Tubulin-Microtubule System: Insights Into the Mechanism of Cacalol.Chemical biology & drug design · 2025Article
- Rapid and Efficient Synthesis of Succinated Thiol Compounds via Maleic Anhydride Derivatization.Molecules (Basel, Switzerland) · 2025Article
- Nrf2-Independent Anti-Inflammatory Effects of Dimethyl Fumarate: Challenges and Prospects in Developing Electrophilic Nrf2 Activators for Neurodegenerative Diseases.Antioxidants (Basel, Switzerland) · 2024Review
- Quantification of the immunometabolite protein modifications S-2-succinocysteine and 2,3-dicarboxypropylcysteine.American journal of physiology. Endocrinology and metabolism · 2024Article
- CP110 and CEP135 Localize Near the Proximal Centriolar Remnants of Mice Spermatozoa.microPublication biology · 2024Article
- Defective function of α-ketoglutarate dehydrogenase exacerbates mitochondrial ATP deficits during complex I deficiency.Redox biology · 2023Article
- The Pleiotropic Effects of Fumarate: From Mitochondrial Respiration to Epigenetic Rewiring and DNA Repair Mechanisms.Metabolites · 2023Review
- Review
- Specific Post-Translational Modifications of VDAC3 in ALS-SOD1 Model Cells Identified by High-Resolution Mass Spectrometry.International journal of molecular sciences · 2022Article
- Changes in S-(2-succinyl)cysteine and advanced glycation end-products levels in mouse tissues associated with aging.Amino acids · 2022Article
- Tubulin posttranslational modifications modify the atypical spermatozoon centriole.microPublication biology · 2022Article
- Mitochondrial DNA alterations underlie an irreversible shift to aerobic glycolysis in fumarate hydratase-deficient renal cancer.Science signaling · 2021Article
- Global chemical modifications comparison of human plasma proteome from two different age groups.Scientific reports · 2020Article
- Succinate Supplement Elicited "Pseudohypoxia" Condition to Promote Proliferation, Migration, and Osteogenesis of Periodontal Ligament Cells.Stem cells international · 2020Article
- Succination of Protein Thiols in Human Brain Aging.Frontiers in aging neuroscience · 2020Review
- Identification of Novel Protein Targets of Dimethyl Fumarate Modification in Neurons and Astrocytes Reveals Actions Independent of Nrf2 Stabilization.Molecular & cellular proteomics : MCP · 2019Article
- Dimethyl fumarate: targeting glycolysis to treat MS.Cell research · 2018Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Protein succination is a stable post-translational modification that occurs when fumarate reacts with cysteine residues to generate 2SC [S-(2-succino)cysteine]. We demonstrate that both α- and β-tubulin are increasingly modified by succination in 3T3-L1 adipocytes and in the adipose tissue of db/db mice. Incubation of purified tubulin from porcine brain with fumarate (50 mM) or the pharmacological compound DMF (dimethylfumarate, 500 μM) inhibited polymerization up to 35% and 59% respectively. Using MS we identified Cys347α, Cys376α, Cys12β and Cys303β as sites of succination in porcine brain tubulin and the relative abundance of succination at these cysteine residues increased in association with fumarate concentration. The increase in succination after incubation with fumarate altered tubulin recognition by an anti-α-tubulin antibody. Succinated tubulin in adipocytes cultured in high glucose compared with normal glucose also had reduced reactivity with the anti-α-tubulin antibody; suggesting that succination may interfere with tubulin-protein interactions. DMF reacted rapidly with 11 of the 20 cysteine residues in the αβ-tubulin dimer, decreased the number of free thiols and inhibited the proliferation of 3T3-L1 fibroblasts. Our data suggest that inhibition of tubulin polymerization is an important undocumented mechanism of action of DMF. Taken together, our results demonstrate that succination is a novel post-translational modification of tubulin and suggest that extensive modification by fumarate, either physiologically or pharmacologically, may alter microtubule dynamics.
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