Quantitative interactome analysis reveals a chemoresistant edgotype
Juan D. Chavez,
Devin K. Schweppe,
Jimmy K. Eng,
Chunxiang Zheng,
Alex Taipale,
Yiyi Zhang,
Kohji Takara and
James E. Bruce ()
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Juan D. Chavez: University of Washington
Devin K. Schweppe: University of Washington
Jimmy K. Eng: University of Washington
Chunxiang Zheng: University of Washington
Alex Taipale: University of Washington
Yiyi Zhang: University of Washington
Kohji Takara: Himeji Dokkoyo University
James E. Bruce: University of Washington
Nature Communications, 2015, vol. 6, issue 1, 1-12
Abstract:
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.
Date: 2015
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8928
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DOI: 10.1038/ncomms8928
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