Universität zu Köln

Liu, Yansheng ORCID: 0000-0002-2626-3912, Borel, Christelle, Li, Li, Mueller, Torsten, Williams, Evan G., Germain, Pierre-Luc, Buljan, Marija, Sajic, Tatjana, Boersema, Paul J., Shao, Wenguang, Faini, Marco, Testa, Giuseppe ORCID: 0000-0002-9104-0918, Beyer, Andreas ORCID: 0000-0002-3891-2123, Antonarakis, Stylianos E. and Aebersold, Ruedi ORCID: 0000-0002-9576-3267 (2017). Systematic proteome and proteostasis profiling in human Trisomy 21 fibroblast cells. Nat. Commun., 8. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Liu, Yansheng UNSPECIFIED orcid.org/0000-0002-2626-3912 UNSPECIFIED Borel, Christelle UNSPECIFIED UNSPECIFIED UNSPECIFIED Li, Li UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Torsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Williams, Evan G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Germain, Pierre-Luc UNSPECIFIED UNSPECIFIED UNSPECIFIED Buljan, Marija UNSPECIFIED UNSPECIFIED UNSPECIFIED Sajic, Tatjana UNSPECIFIED UNSPECIFIED UNSPECIFIED Boersema, Paul J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Shao, Wenguang UNSPECIFIED UNSPECIFIED UNSPECIFIED Faini, Marco UNSPECIFIED UNSPECIFIED UNSPECIFIED Testa, Giuseppe UNSPECIFIED orcid.org/0000-0002-9104-0918 UNSPECIFIED Beyer, Andreas UNSPECIFIED orcid.org/0000-0002-3891-2123 UNSPECIFIED Antonarakis, Stylianos E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Aebersold, Ruedi UNSPECIFIED orcid.org/0000-0002-9576-3267 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-213817
DOI:	10.1038/s41467-017-01422-6
Journal or Publication Title:	Nat. Commun.
Volume:	8
Date:	2017
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2041-1723
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GENE-EXPRESSION VARIATION; DOWN-SYNDROME; MITOCHONDRIAL DYSFUNCTION; PEPTIDE IDENTIFICATION; QUANTIFICATION; CHROMOSOME-21; DEGRADATION; DYNAMICS; REVEALS; DOSAGE Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21381