biostudies-literaturePiroli GGNICHD NIH HHSNIDDK NIH HHSNIGMS NIH HHS231-45https://www.ebi.ac.uk/biostudies/studies/S-EPMC4324573biostudies-literatureUnknown462(2)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 tubThe Biochemical journalIdentification of protein succination as a novel modification of tubulin.PMC4324573P20 GM109091R37 DK019971R03 HD077187DK-19971Tanis RMJepson MJBrock JWFrizzell NManuel AMRajesh MPWalla MDPiroli GGCotham WEfalseIdentification of protein succination as a novel modification of tubulin.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 tub2014-01-01T00:00:00Z2014 Sep2025-04-19T16:46:40.654Z2020-11-19T08:14:13ZS-EPMC43245732490964110.1042/bj2013158110.1042/BJ20131581