Systematic proteome and proteostasis profiling in human Trisomy 21 fibroblast cells

Yansheng Liu, Christelle Borel, Li Li, Torsten Müller, Evan G. Williams, Pierre-Luc Germain, Marija Buljan, Tatjana Sajic, Paul J. Boersema, Wenguang Shao, Marco Faini, Giuseppe Testa, Andreas Beyer (), Stylianos E. Antonarakis () and Ruedi Aebersold ()
Additional contact information
Yansheng Liu: Institute of Molecular Systems Biology, ETH Zurich
Christelle Borel: University of Geneva Medical School, and University Hospitals of Geneva
Li Li: University of Cologne, CECAD, University of Cologne
Torsten Müller: Institute of Molecular Systems Biology, ETH Zurich
Evan G. Williams: Institute of Molecular Systems Biology, ETH Zurich
Pierre-Luc Germain: European Institute of Oncology
Marija Buljan: Institute of Molecular Systems Biology, ETH Zurich
Tatjana Sajic: Institute of Molecular Systems Biology, ETH Zurich
Paul J. Boersema: Institute of Biochemistry, Department of Biology, ETH Zurich
Wenguang Shao: Institute of Molecular Systems Biology, ETH Zurich
Marco Faini: Institute of Molecular Systems Biology, ETH Zurich
Giuseppe Testa: European Institute of Oncology
Andreas Beyer: University of Cologne, CECAD, University of Cologne
Stylianos E. Antonarakis: University of Geneva Medical School, and University Hospitals of Geneva
Ruedi Aebersold: Institute of Molecular Systems Biology, ETH Zurich

Nature Communications, 2017, vol. 8, issue 1, 1-15

Abstract: Abstract Down syndrome (DS) is mostly caused by a trisomy of the entire Chromosome 21 (Trisomy 21, T21). Here, we use SWATH mass spectrometry to quantify protein abundance and protein turnover in fibroblasts from a monozygotic twin pair discordant for T21, and to profile protein expression in 11 unrelated DS individuals and matched controls. The integration of the steady-state and turnover proteomic data indicates that protein-specific degradation of members of stoichiometric complexes is a major determinant of T21 gene dosage outcome, both within and between individuals. This effect is not apparent from genomic and transcriptomic data. The data also reveal that T21 results in extensive proteome remodeling, affecting proteins encoded by all chromosomes. Finally, we find broad, organelle-specific post-transcriptional effects such as significant downregulation of the mitochondrial proteome contributing to T21 hallmarks. Overall, we provide a valuable proteomic resource to understand the origin of DS phenotypic manifestations.

Date: 2017
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-017-01422-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01422-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-017-01422-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().