Reference : PPARγ population shift produces disease-related changes in molecular networks associa...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Human health sciences : Endocrinology, metabolism & nutrition
Human health sciences : Cardiovascular & respiratory systems
http://hdl.handle.net/10993/4559
PPARγ population shift produces disease-related changes in molecular networks associated with metabolic syndrome
English
Jurkowski, Wiktor [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Roomp, Kirsten mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Crespo, Isaac mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Schneider, Jochen mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
del Sol Mesa, Antonio mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
2011
Cell Death & Disease
Nature Publishing Group
2
8
e192
Yes (verified by ORBilu)
International
2041-4889
London
UK
[en] metabolic syndrome ; PPARγ ; protein population shift ; bi-stable switches ; disease-related networks
[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.
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)
http://hdl.handle.net/10993/4559
10.1038/cddis.2011.74
e192

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