Description
Sieber J, Wieder N, Clark A, Reitberger M, Matan S, Schoenfelder J, Zhang J, Mandinova A, Bittker JA, Gutierrez J, Aygun O, Udeshi N, Carr SA, Mundel P, Jehle AW, and Greka A. Cell Chem Bio 2017. Progressive kidney diseases affect approximately 500 million people worldwide. Podocytes are terminally differentiated cells of the kidney filter, whose loss leads to disease progression and kidney failure. To date, there are no therapies to promote podocyte survival. Drug repurposing may therefore help accelerate the development of cures in an area of tremendous unmet need. In a newly developed high-throughput screening assay of podocyte viability, we identified the BRAF V600E inhibitor GDC-0879 and the adenylate cyclase agonist forskolin as podocyte survival promoting compounds. GDC-0879 protects podocytes from injury through paradoxical activation of the MEK/ERK pathway. Forskolin promotes podocyte survival by attenuating protein biosynthesis. Importantly, GDC-0879 and forskolin are shown to promote podocyte survival against an array of cellular stressors. This work reveals new therapeutic targets for much needed podocyte-protective therapies, and provides insights into the use of GDC-0879-like molecules for the treatment of progressive kidney diseases.
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: kidney ; TMT
Contact
Principal Investigators:
(in alphabetical order)
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Steven A. Carr, Broad Institute of MIT and Harvard, United States
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Submitting User: |
clauser
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Number of distinct conditions across all analyses (original submission and reanalyses)
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Distinct condition labels are counted across all files submitted in the "Metadata" category
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Number of distinct biological replicates across all analyses (original submission and reanalyses)
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Distinct replicate labels are counted across all files submitted in the "Metadata" category
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Originally identified proteins that were automatically
remapped by MassIVE to proteins in the
SwissProt
human reference database.
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Number of distinct protein accessions reported across all analyses (original submission and
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Number of distinct unmodified peptide sequences reported across all analyses (original
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Number of distinct peptide sequences (including modified variants or peptidoforms) reported
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Total number of peptide-spectrum matches (i.e. spectrum identifications) reported across all
analyses (original submission and reanalyses) associated with this dataset.
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Number of distinct proteins quantified across all analyses (original submission and reanalyses)
associated with this dataset.
Distinct protein accessions are counted across all files submitted in the "Statistical Analysis
of Quantified Analytes" category having a "Protein" column in this dataset.
"N/A" means no results of this type were submitted.
Number of distinct proteins found to be differentially abundant in at least one comparison
across all analyses (original submission and reanalyses) associated with this dataset.
A protein is differentially abundant if its change in abundance across conditions is found
to be statistically significant with an adjusted p-value <= 0.05 and lists no issues associated
with statistical tests for differential abundance.
Distinct protein accessions are counted across all files submitted in the "Statistical Analysis
of Quantified Analytes" category having a "Protein" column in this dataset.
"N/A" means no results of this type were submitted.
This dataset may not contain all raw spectra data as originally deposited in PRIDE.
It has been imported to MassIVE for reanalysis purposes, so its spectra data here may
consist solely of processed peak lists suitable for reanalysis with most software.