title: Treating Colon Cancer Cells with FK228 Reveals a Link between Histone Lysine Acetylation and Extensive Changes in the Cellular Proteome.
abstract: The therapeutic value of FK228 as a cancer treatment option is well known, and various types of cancer have been shown to respond to this drug. However, the complete mechanism of FK228 and the affect it has on histone lysine acetylation and the colon cancer cell proteome are largely unknown. In the present study, we used stable isotope labeling by amino acids in cell culture (SILAC) and affinity enrichment followed by high-resolution liquid chromatograph-mass spectrometer (LC-MS)/MS analysis to quantitate the changes in the lysine acetylome in HCT-8 cells after FK228 treatment. A total of 1,194 lysine acetylation sites in 751 proteins were quantified, with 115 of the sites in 85 proteins being significantly upregulated and 38 of the sites in 32 proteins being significantly downregulated in response to FK228 treatment. Interestingly, 47 histone lysine acetylation sites were identified in the core histone proteins. We also found a novel lysine acetylation site on H2BK121. These significantly altered proteins are involved in multiple biological functions as well as a myriad of metabolic and enzyme-regulated pathways. Taken together, the link between FK228 function and the downstream changes in the HCT-8 cell proteome observed in response to FK228 treatment is established.
authors.affiliation: Department of Biochemistry and Molecular Biology, Xinxiang Medical University, Xinxiang 453003, Henan, China.|Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang 453003, China.
authors.forename: Tian-yun
authors.initials: TY
authors.lastname: Wang
authors.affiliation: Pharmacy Collage, Xinxiang Medical University, Xinxiang 453003, Henan, China.
authors.forename: Yan-long
authors.initials: YL
authors.lastname: Jia
authors.affiliation: Department of Biochemistry and Molecular Biology, Xinxiang Medical University, Xinxiang 453003, Henan, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Xinxiang Medical University, Xinxiang 453003, Henan, China.
authors.forename: Qiu-li
authors.initials: QL
authors.lastname: Sun
authors.affiliation: Department of Biochemistry and Molecular Biology, Xinxiang Medical University, Xinxiang 453003, Henan, China.|Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang 453003, China.
authors.forename: Yi-chun
authors.initials: YC
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Xinxiang Medical University, Xinxiang 453003, Henan, China.
authors.forename: Jun-he
authors.initials: JH
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Xinxiang Medical University, Xinxiang 453003, Henan, China.
authors.forename: Chun-peng
authors.initials: CP
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Molecular Biology, Xinxiang Medical University, Xinxiang 453003, Henan, China.
authors.forename: Xiao-yin
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Xinxiang Medical University, Xinxiang 453003, Henan, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002853:Chromatography, Liquid; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D047630:Depsipeptides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007553:Isotope Labeling; D008239:Lysine / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D053719:Tandem Mass Spectrometry
chemical_list: D000903:Antibiotics, Antineoplastic; D047630:Depsipeptides; D006657:Histones; D020543:Proteome; C087123:romidepsin; D008239:Lysine