Quantitative interactome analysis reveals a chemoresistant edgotype View Full Text


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Article Info

DATE

2015-08-03

AUTHORS

Juan D. Chavez, Devin K. Schweppe, Jimmy K. Eng, Chunxiang Zheng, Alex Taipale, Yiyi Zhang, Kohji Takara, James E. Bruce

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. More... »

PAGES

7928

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ncomms8928

    DOI

    http://dx.doi.org/10.1038/ncomms8928

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1039967099

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/26235782


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