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Series GSE59354 Query DataSets for GSE59354
Status Public on May 01, 2015
Title Dual regulation of Fbw7 function and oncogenic transformation by Usp28
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Fbw7, the substrate recognition subunit of SCF(Fbw7) ubiquitin ligase, mediates turnover of multiple proto-oncoproteins and promotes its own degradation. Fbw7-mediated substrate degradation is antagonized by the Usp28 deubiquitinase. We now show, using knockout mice, that Usp28 preferentially deubiquitinates and stabilizes Fbw7. Monoallelic deletion of Usp28 maintains stable Fbw7 but destabilizes Fbw7 substrates. In contrast, complete knockout of Usp28 promotes Pin1-dependent autocatalytic turnover of Fbw7, accumulation of Fbw7 substrates and oncogenic transformation. Overexpression of Usp28 stabilizes both Fbw7 and its substrates and similarly enhances transformation. We propose that dual regulation of Fbw7 activity by Usp28 maintains physiological levels of Fbw7 substrates, and that both loss and overexpression of Usp28 in human cancer promote Fbw7 substrate accumulation.
Overall design RNAseq experiments of E13.5 murine embryonic fibroblasts (MEFs) derived from animals in which Usp28 was either deleted (-/-), wildtype (+/+) or heterozygous (+/-). In a first set of experiments immortalized MEFs of all three genotypes were analysed in biological triplicates. In a second set of experiments immortalized and Ras transformed MEFs of all three genotypes and MEFs which overexpress USP28 (+/+/+) where sequenced in duplicates.
Contributor(s) Schülein-Völk C, Zhu J, Xu W, Taranets L, Hellmann A, Wolf E, Eilers M, Popov N
Citation(s) 25437563
Submission date Jul 11, 2014
Last update date May 15, 2019
Contact name Martin Eilers
Organization name University of Wuerzburg
Department Chair for Biochemistry and Molecular Biology
Lab Martin Eilers
Street address Am Hubland
City Wuerzburg
ZIP/Postal code 97074
Country Germany
Platforms (1)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
Samples (17)
GSM1435567 plus-plus-1
GSM1435568 plus-plus-2
GSM1435569 plus-plus-3
BioProject PRJNA255128
SRA SRP044274

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Supplementary file Size Download File type/resource
GSE59354_diff_exp_masterfile.txt.gz 1.9 Mb (ftp)(http) TXT
GSE59354_regulation.txt.gz 946.9 Kb (ftp)(http) TXT
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