Article (Scientific journals)
PPARγ population shift produces disease-related changes in molecular networks associated with metabolic syndrome
Jurkowski, Wiktor; Roomp, Kirsten; Crespo, Isaac et al.
2011In Cell Death and Disease, 2 (8), p. 192
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Keywords :
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 center :
- 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)
Disciplines :
Endocrinology, metabolism & nutrition
Biochemistry, biophysics & molecular biology
Cardiovascular & respiratory systems
Identifiers :
UNILU:UL-ARTICLE-2011-435
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
External co-authors :
no
Language :
English
Title :
PPARγ population shift produces disease-related changes in molecular networks associated with metabolic syndrome
Publication date :
2011
Journal title :
Cell Death and Disease
ISSN :
2041-4889
Publisher :
Nature Publishing Group, London, United Kingdom
Volume :
2
Issue :
8
Pages :
e192
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
e192
Available on ORBilu :
since 03 August 2013

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