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Series GSE52667 Query DataSets for GSE52667
Status Public on Apr 24, 2015
Title The FoxO signature in protein breakdown
Organism Mus musculus
Experiment type Expression profiling by array
Summary Under stress conditions mammalian cells activate compensatory mechanisms to survive and maintain cellular function. During catabolic conditions, such as low nutrients, systemic inflammation, cancer or infections, protein breakdown is enhanced and aminoacids are released from muscles to sustain liver gluconeogenesis and tissues protein synthesis. Proteolysis in muscle is orchestrated by a set of genes named atrophy-related genes. A system that is activated both in short and prolonged stress conditions is the family of Forkhead Box (Fox) O transcription factors. Here, we report that muscle-specific deletion of FoxO members resulted in protection from muscle loss because FoxO family is required for induction of autophagy-lysosome and ubiquitin-proteasome systems. Importantly, FoxOs are required for Akt activity but not for mTOR signalling underlining the concept that FoxOs are upstream mTOR for the control of protein breakdown when nutrients are lacking. Moreover, FoxO family controls the induction of critical genes belonging to several fundamental stress response pathways such as unfolded protein response, ROS detoxification and translational regulation. Finally, we identify a set of novel FoxO-dependent ubiquitin ligases including the recent discovered MUSA11 and a new one, which we named Specific of Muscle Atrophy and Regulated by Transcription (SMART). Our findings identify the critical role of FoxO in regulating a variety of genes belonging to pathways important for stress-response under catabolic conditions.
Gene expression in muscles of muscle-specific FoxO 1,3,4 knock-out mice that were fed normally or starved
Overall design We generated knocked-out FoxO 1,3,4 specifically in muscle by crossing FoxO1-3-4-floxed mice (FoxO1,3,4 f/f) with a transgenic line expressing Cre recombinase under the control of MLC1f promoter to generate muscle-specific FoxO1,3,4 triple knockout mice. These mice were either fed ad libitum or starved. Subsequently gene expression of the gastrocnemius muscles was analyzed.
For each of the 4 conditions (FOXO1,3,4 f/f fed or starved, FOXO1,3,4-/- fed or starved), we isolated the gastrocnemius muscles of 3 mice thus yielding 6 muscles per condition.
RNA was prepared from these muscles using the TRIzol method (Life Technologies) followed by cleanup with the RNeasy kit (QIAGEN). RNA concentration was determined by spectrophotometry and quality of the RNA was monitored using the Agilent 2100 Bioanalyzer (Agilent Technologies). RNA of the 6 muscles per condition was pooled equimolarly and used for further microarray analysis. cRNA was prepared, labelled and hybridised to Affymetrix Mouse Genome 430 2.0 Arrays using Affymetrix-supplied kits and according to standard Affymetrix protocols. Expression values were summarized using the Mas 5.0 algorithm. Genes that were up- or downregulated upon starvation compared to the fed condition were determined using Excel software. A threshold of 1.5 was used for the fold up-or downregulation consistent with the fold change that can be reliably detected with these type of arrays.
Contributor(s) Sandri M, Abraham R, Milan G, Romanello V, Pescatore F, Armani A, Paik J, Frasson L, Seydel A, Zhao J, Goldberg AL, Blaauw B, Depinho R, Crosariol M
Citation(s) 25858807
Submission date Nov 22, 2013
Last update date Feb 11, 2019
Contact name Marco Sandri
Organization name University of Padova
Department Department of Biomedical Science
Street address Viale Colombo 3
City Padova
ZIP/Postal code 35121
Country Italy
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (4)
GSM1273848 wild type, fed
GSM1273849 wild type, starved
GSM1273850 Foxo 1,3,4 muscle specific knock-out, fed
BioProject PRJNA229763

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE52667_RAW.tar 14.0 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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