title: Quantitative interactome analysis reveals a chemoresistant edgotype.
abstract: Chemoresistance is a common mode of therapy failure for many cancers. Tumours develop resistance to chemotherapeutics through a variety of mechanisms, with proteins serving pivotal roles. Changes in protein conformations and interactions affect the cellular response to environmental conditions contributing to the development of new phenotypes. The ability to understand how protein interaction networks adapt to yield new function or alter phenotype is limited by the inability to determine structural and protein interaction changes on a proteomic scale. Here, chemical crosslinking and mass spectrometry were employed to quantify changes in protein structures and interactions in multidrug-resistant human carcinoma cells. Quantitative analysis of the largest crosslinking-derived, protein interaction network comprising 1,391 crosslinked peptides allows for 'edgotype' analysis in a cell model of chemoresistance. We detect consistent changes to protein interactions and structures, including those involving cytokeratins, topoisomerase-2-alpha, and post-translationally modified histones, which correlate with a chemoresistant phenotype.
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Juan D
authors.initials: JD
authors.lastname: Chavez
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Devin K
authors.initials: DK
authors.lastname: Schweppe
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Jimmy K
authors.initials: JK
authors.lastname: Eng
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Taipale
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Yiyi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Sciences, Himeji Dokkoyo University, Himeji, Hyogo 670-8524, Japan.
authors.forename: Kohji
authors.initials: K
authors.lastname: Takara
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Bruce
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism; D015153:Blotting, Western; D002277:Carcinoma / Q000378:metabolism*; D002853:Chromatography, Liquid; D004260:DNA Repair; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D006367:HeLa Cells; D042421:Histone Code; D006657:Histones / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D007633:Keratins / Q000378:metabolism; D013058:Mass Spectrometry; D008856:Microscopy, Fluorescence; D010641:Phenotype; D060066:Protein Interaction Maps; D002583:Uterine Cervical Neoplasms / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D006657:Histones; D007633:Keratins; D004250:DNA Topoisomerases, Type II