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PPARγ population shift produces disease-related changes in molecular networks associated with metabolic syndrome.

Abstract：

: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.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Jurkowski W,Roomp K,Crespo I,Schneider JG,Del Sol A

doi

10.1038/cddis.2011.74

subject

Has Abstract

pub_date

2011-08-11 00:00:00

pages

e192

issn

2041-4889

pii

cddis201174

journal_volume

2

pub_type

杂志文章

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