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Series GSE156346 Query DataSets for GSE156346
Status Public on Aug 15, 2022
Title Modulation of protease expression by PITX transcription factors regulates protein quality control during aging
Organism Drosophila melanogaster
Experiment type Expression profiling by high throughput sequencing
Third-party reanalysis
Summary Protein quality control is important for healthy aging and is dysregulated in several age-related diseases. The autophagy-lysosome and ubiquitin-proteasome systems are key for proteostasis but it remains largely unknown whether other proteolytic systems maintain protein quality control during aging. Here, we find that the expression of proteolytic enzymes (proteases/peptidases) distinct from the autophagy-lysosome and ubiquitin-proteasome systems declines during skeletal muscle aging in Drosophila. Age-dependent downregulation of proteases undermines proteostasis, as demonstrated by the increase in detergent-insoluble poly-ubiquitinated proteins and pathogenic huntingtin-polyQ in response to protease RNAi. Transcriptomic analysis identifies Ptx1, homologous to human PITX1/2/3, as a transcriptional regulator of proteases. Specifically, RNAi for Ptx1 increases the expression of age-downregulated proteases and improves protein quality. Moreover, muscle-specific expression of Ptx1 RNAi extends lifespan. These findings indicate that protein quality control is ensured during aging by autophagy/proteasome-independent proteases that degrade misfolded and aggregation-prone proteins and by their transcriptional modulator Ptx1.
 
Overall design Here 3 Drosophila melanogaster RNA seq samples treated with Pitx RNAi are compred to control samples from GSE149799: GSM4512833 FD_GFP_1TH GSM4512834 FD_GFP_2TH GSM4512835 FD_GFP_3TH GSM4512836 FD_white_1TH GSM4512837 FD_white_2TH GSM4512838 FD_white_3TH
 
Contributor(s) Jiao J, Curley M, Zuanazzi FG, Robles-Murguia M, Shirinifard A, Finkelstein D, Xu B, Fan Y, Demontis F
Citation(s) 36640359
Submission date Aug 17, 2020
Last update date Jan 23, 2023
Contact name David Finkelstein
E-mail(s) david.finkelstein@stjude.org
Phone 9014953931
Organization name St Jude Children's Research Hospital
Department Computational Biology
Street address 332 N. Lauderdale St.
City Memphis
State/province TN
ZIP/Postal code 38105
Country USA
 
Platforms (1)
GPL13304 Illumina HiSeq 2000 (Drosophila melanogaster)
Samples (3)
GSM4729345 MhcGal4PtxRNAi2_sample1
GSM4729346 MhcGal4PtxRNAi2_sample2
GSM4729347 MhcGal4PtxRNAi2_sample3
Relations
Reanalysis of GSM4512833
Reanalysis of GSM4512834
Reanalysis of GSM4512835
Reanalysis of GSM4512836
Reanalysis of GSM4512837
Reanalysis of GSM4512838
BioProject PRJNA657572
SRA SRP277815

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
GSE156346_RAW.tar 220.0 Kb (http)(custom) TAR (of TXT)
GSE156346_counts.GSM4512833.txt.gz 70.0 Kb (ftp)(http) TXT
GSE156346_counts.GSM4512834.txt.gz 69.3 Kb (ftp)(http) TXT
GSE156346_counts.GSM4512835.txt.gz 69.2 Kb (ftp)(http) TXT
GSE156346_counts.GSM4512836.txt.gz 70.0 Kb (ftp)(http) TXT
GSE156346_counts.GSM4512837.txt.gz 69.6 Kb (ftp)(http) TXT
GSE156346_counts.GSM4512838.txt.gz 69.5 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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