title: Large-Scale Identification of Protein Crotonylation Reveals Its Role in Multiple Cellular Functions.
abstract: Lysine crotonylation on histones is a recently identified post-translational modification that has been demonstrated to associate with active promoters and to directly stimulate transcription. Given that crotonyl-CoA is essential for the acyl transfer reaction and it is a metabolic intermediate widely localized within the cell, we postulate that lysine crotonylation on nonhistone proteins could also widely exist. Using specific antibody enrichment followed by high-resolution mass spectrometry analysis, we identified hundreds of crotonylated proteins and lysine residues. Bioinformatics analysis reveals that crotonylated proteins are particularly enriched for nuclear proteins involved in RNA processing, nucleic acid metabolism, chromosome organization, and gene expression. Furthermore, we demonstrate that crotonylation regulates HDAC1 activity, expels HP1α from heterochromatin, and inhibits cell cycle progression through S-phase. Our data thus indicate that lysine crotonylation could occur in a large number of proteins and could have important regulatory roles in multiple nuclei-related cellular processes.
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University , Shanghai 200241, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University , Shanghai 200241, China.
authors.forename: Anqi
authors.initials: A
authors.lastname: Mao
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University , Shanghai 200241, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Tang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University , Shanghai 200241, China.
authors.forename: Qiufang
authors.initials: Q
authors.lastname: Zeng
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University , Shanghai 200241, China.
authors.forename: Shennan
authors.initials: S
authors.lastname: Gao
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University , Shanghai 200241, China.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University , Shanghai 200241, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University , Shanghai 200241, China.
authors.forename: Wenpeng
authors.initials: W
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University , Shanghai 200241, China.
authors.forename: James X
authors.initials: JX
authors.lastname: Du
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University , Shanghai 200241, China.
authors.forename: Jiwen
authors.initials: J
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University , Shanghai 200241, China.|Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center , Guangzhou 510060, China.
authors.forename: Jiemin
authors.initials: J
authors.lastname: Wong
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University , Shanghai 200241, China.
authors.forename: Lujian
authors.identifier: 0000-0001-7021-5582
authors.initials: L
authors.lastname: Liao
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000302:isolation & purification / Q000378:metabolism*; D000090266:Chromobox Protein Homolog 5; D004261:DNA Replication / Q000235:genetics; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D040901:Proteomics
chemical_list: D000214:Acyl Coenzyme A; C000715594:CBX5 protein, human; D018797:Cell Cycle Proteins; D006657:Histones; D000090266:Chromobox Protein Homolog 5; C010701:crotonyl-coenzyme A; D008239:Lysine
keywords: DNA replication; cell cycle; lysine crotonylation; mass spectrometry; proteomics