BioProject

Secreted proteins serve pivotal roles in the development of multicellular organisms, acting as structural matrix, extracellular enzymes and signal molecules. More...

Secreted proteins serve pivotal roles in the development of multicellular organisms, acting as structural matrix, extracellular enzymes and signal molecules. In this study we demonstrate, unexpectedly, that PGC-1α, a critical transcriptional co-activator of metabolic gene expression, functions to down-regulate expression of diverse genes encoding secreted molecules and extracellular matrix (ECM) components to modulate the secretome. We show that both endogenous and exogenous PGC-1α down-regulate expression of numerous genes encoding secreted molecules. Mechanistically, results obtained using mRNA stability measurements as well as intronic RNA expression analysis are consistent with a transcriptional effect of PGC-1α on expression of genes encoding secreted proteins. Interestingly, PGC-1α requires the central heat shock response regulator HSF1 to affect some of its targets, and both factors co-reside on several target genes encoding secreted molecules in cells. Finally, using a mass spectrometric analysis of secreted proteins, we demonstrate that PGC-1α modulates the secretome of mouse embryonic fibroblasts (MEFs). Overall design: Cells were grown in 12-well plates and control adenoviruses (Ad-control) or PGC-1alpha (Ad-PGC-1α) encoding adenoviruses were directly added to the culture medium where indicated. PGC-1α KO and PGC-1α WT differentiated brown adipocytes were examined. Less...