Reference : PPARγ population shift produces disease-related changes in molecular networks associa...

	Document type :	Scientific journals : Article
	Discipline(s) :	Life sciences : Biochemistry, biophysics & molecular biology Human health sciences : Endocrinology, metabolism & nutrition Human health sciences : Cardiovascular & respiratory systems
	To cite this reference:	http://hdl.handle.net/10993/4559

Title :	PPARγ population shift produces disease-related changes in molecular networks associated with metabolic syndrome
Language :	English
Author, co-author :	Jurkowski, Wiktor [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
	Roomp, Kirsten [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
	Crespo, Isaac [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
	Schneider, Jochen [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
	del Sol Mesa, Antonio [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Publication date :	2011
Journal title :	Cell Death and Disease
Publisher :	Nature Publishing Group
Volume :	2
Issue/season :	8
Pages :	e192
Peer reviewed :	Yes (verified by ORBilu)
Audience :	International
e-ISSN :	2041-4889
City :	London
Country :	UK
Keywords :	[en] metabolic syndrome ; PPARγ ; protein population shift ; bi-stable switches ; disease-related networks
Abstract :	[en] Peroxisome proliferator-activated receptor gamma (PPARγ) is a key regulator of adipocyte differentiation and has an important role in metabolic syndrome. Phosphorylation of the receptor's ligand-binding domain at serine 273 has been shown to change the expression of a large number of genes implicated in obesity. The difference in gene expression seen when comparing wild-type phosphorylated with mutant non-phosphorylated PPARγ may have important consequences for the cellular molecular network, the state of which can be shifted from the healthy to a stable diseased state. We found that a group of differentially expressed genes are involved in bi-stable switches and form a core network, the state of which changes with disease progression. These findings support the idea that bi-stable switches may be a mechanism for locking the core gene network into a diseased state and for efficiently propagating perturbations to more distant regions of the network. A structural analysis of the PPARγ-RXRα dimer complex supports the hypothesis of a major structural change between the two states, and this may represent an important mechanism leading to the differential expression observed in the core network.
Research centres :	Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) ; Luxembourg Centre for Systems Biomedicine (LCSB): Computational Biology (Del Sol Group) ; Luxembourg Centre for Systems Biomedicine (LCSB): Medical Translational Research (J. Schneider Group)
Permalink :	http://hdl.handle.net/10993/4559
DOI :	10.1038/cddis.2011.74
Commentary :	e192

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