title: Crosstalk among the proteome, lysine phosphorylation, and acetylation in romidepsin-treated colon cancer cells.
abstract: Romidepsin (FK228) is one of the most promising histone-deacetylase inhibitors due to its potent antitumor activity, and has been used as a practical option for cancer therapy. However, FK228-induced changes in protein modifications and the crosstalk between different modifications has not been reported. To better understand the underlying mechanisms of FK228-related cancer therapy, we investigated the acetylome, phosphorylation, and crosstalk between modification datasets in colon cancer cells treated with FK228 by using stable-isotope labeling with amino acids in cell culture and affinity enrichment, followed by high-resolution liquid chromatography tandem mass spectrometry analysis. In total, 2728 protein groups, 1175 lysine-acetylation sites, and 4119 lysine-phosphorylation sites were quantified. When the quantification ratio thresholds were set to > 2.0 and < 0.5, respectively, a total of 115 and 38 lysine-acetylation sites in 85 and 32 proteins were quantified as increased and decreased targets, respectively, and 889 and 370 lysine-phosphorylation sites in 599 and 289 proteins were quantified as increased and decreased targets, respectively. Furthermore, we identified 274 proteins exhibiting both acetylation and phosphorylation modifications. These findings indicated possible involvement of these proteins in FK228-related treatment of colon cancer, and provided insight for further analysis of their biological function.
authors.affiliation: Department of Biochemistry and Molecular Biology, Xinxiang Medical University, Henan, 453003, China.|Henan Collaborative Innovation Canter of Molecular Diagnosis and Laboratory Medicine, Xinxiang, Henan, 453003, China.
authors.forename: Tian-Yun
authors.initials: TY
authors.lastname: Wang
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, China.
authors.forename: Yu-Rong
authors.initials: YR
authors.lastname: Chai
authors.affiliation: Pharmacy Collage, Xinxiang Medical University, Xinxiang, Henan, 453003, China.
authors.forename: Yan-Long
authors.initials: YL
authors.lastname: Jia
authors.affiliation: Henan Collaborative Innovation Canter of Molecular Diagnosis and Laboratory Medicine, Xinxiang, Henan, 453003, China.
authors.forename: Jian-Hui
authors.initials: JH
authors.lastname: Gao
authors.affiliation: Jingjie PTM BioLab (Hangzhou) Co. Ltd, Hangzhou, 310018, China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Peng
authors.affiliation: Jingjie PTM BioLab (Hangzhou) Co. Ltd, Hangzhou, 310018, China.
authors.forename: Hua-Feng
authors.initials: HF
authors.lastname: Han
mesh_terms: D000107:Acetylation; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism*; D047630:Depsipeptides / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D008239:Lysine / Q000378:metabolism; D010766:Phosphorylation; D020543:Proteome / Q000187:drug effects*; D020239:Receptor Cross-Talk / Q000187:drug effects*
chemical_list: D000903:Antibiotics, Antineoplastic; D047630:Depsipeptides; D056572:Histone Deacetylase Inhibitors; D020543:Proteome; C087123:romidepsin; D008239:Lysine
keywords: colon cancer; histone lysine-acetylation; histone lysine-phosphorylation; proteome; romidepsin