Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Molecular and genetic crosstalks between mTOR and ERRα are key determinants of rapamycin-induced nonalcoholic fatty liver.

Cell metabolism | Apr 2, 2013

mTOR and ERRα are key regulators of common metabolic processes, including lipid homeostasis. However, it is currently unknown whether these factors cooperate in the control of metabolism. ChIP-sequencing analyses of mouse liver reveal that mTOR occupies regulatory regions of genes on a genome-wide scale including enrichment at genes shared with ERRα that are involved in the TCA cycle and lipid biosynthesis. Genetic ablation of ERRα and rapamycin treatment, alone or in combination, alter the expression of these genes and induce the accumulation of TCA metabolites. As a consequence, both genetic and pharmacological inhibition of ERRα activity exacerbates hepatic hyperlipidemia observed in rapamycin-treated mice. We further show that mTOR regulates ERRα activity through ubiquitin-mediated degradation via transcriptional control of the ubiquitin-proteasome pathway. Our work expands the role of mTOR action in metabolism and highlights the existence of a potent mTOR/ERRα regulatory axis with significant clinical impact.

Pubmed ID: 23562079 RIS Download

Mesh terms: Animals | Chromatin Immunoprecipitation | Citric Acid Cycle | Fatty Liver | Gene Regulatory Networks | HeLa Cells | High-Throughput Nucleotide Sequencing | Humans | Lipid Metabolism | Male | Mice | Mice, Inbred C57BL | Mice, Knockout | Non-alcoholic Fatty Liver Disease | Proteasome Endopeptidase Complex | Protein Interaction Maps | Receptors, Estrogen | Signal Transduction | Sirolimus | TOR Serine-Threonine Kinases | Transcription, Genetic | Ubiquitin

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


Gene Expression Omnibus

Functional genomics data repository supporting MIAME-compliant data submissions. Tools are provided to help users query and download experiments and curated gene expression profiles. These data include microarray-based experiments measuring the abundance of mRNA, genomic DNA, and protein molecules, as well as non-array-based technologies such as serial analysis of gene expression (SAGE) and mass spectrometry proteomic technology. Array- and sequence-based data are accepted.

tool

View all literature mentions