Reference : Systematic proteome and proteostasis profiling in human Trisomy 21 fibroblast cells.
Scientific journals : Article
Life sciences : Genetics & genetic processes
http://hdl.handle.net/10993/43146
Systematic proteome and proteostasis profiling in human Trisomy 21 fibroblast cells.
English
Liu, Yansheng [> >]
Borel, Christelle [> >]
Li, Li [> >]
Muller, Torsten [> >]
Williams, Evan mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Germain, Pierre-Luc [> >]
Buljan, Marija [> >]
Sajic, Tatjana [> >]
Boersema, Paul J. [> >]
Shao, Wenguang [> >]
Faini, Marco [> >]
Testa, Giuseppe [> >]
Beyer, Andreas [> >]
Antonarakis, Stylianos E. [> >]
Aebersold, Ruedi [> >]
2017
Nature communications
8
1
1212
Yes (verified by ORBilu)
2041-1723
2041-1723
England
[en] Databases, Protein ; Dosage Compensation, Genetic ; Fibroblasts/metabolism/pathology ; Gene Expression Regulation ; Humans ; Mitochondrial Proteins/genetics/metabolism ; Organelles/metabolism ; Proteolysis ; Proteome/metabolism ; Proteostasis/genetics ; Signal Transduction ; Trisomy/genetics/pathology
[en] 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.
http://hdl.handle.net/10993/43146
10.1038/s41467-017-01422-6

File(s) associated to this reference

Fulltext file(s):

FileCommentaryVersionSizeAccess
Open access
A_FINAL_PAPER.pdfPublisher postprint1.89 MBView/Open

Bookmark and Share SFX Query

All documents in ORBilu are protected by a user license.