Author
Listed:
- 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)
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.
Suggested Citation
Juan D. Chavez & Devin K. Schweppe & Jimmy K. Eng & Chunxiang Zheng & Alex Taipale & Yiyi Zhang & Kohji Takara & James E. Bruce, 2015.
"Quantitative interactome analysis reveals a chemoresistant edgotype,"
Nature Communications, Nature, vol. 6(1), pages 1-12, November.
Handle:
RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8928
DOI: 10.1038/ncomms8928
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