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Series GSE88871 Query DataSets for GSE88871
Status Public on Jul 24, 2017
Title SPOP mutation confers intrinsic BET inhibitor resistance in prostate cancer (ChIP-Seq)
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Bromodomain and extraterminal domain (BET) protein inhibitors are emerging as promising therapeutics of cancers including prostate cancer. The E3 ubiquitin ligase adaptor protein speckle-type POZ protein (SPOP) is implicated in human prostate cancers due to its frequent mutation. Here we demonstrate that SPOP binds to the BET proteins BRD2, BRD3 and BRD4. Wild-type SPOP, but not prostate cancer-associated mutants, promotes polyubiquitination and proteasome degradation of BET proteins by recognizing a common degron motif. BET protein levels are highly elevated in SPOP-mutated prostate cancers in patients. Expression of cancer-derived SPOP mutants upregulates cholesterol biosynthesis genes and confers resistance to the BET inhibitor in cultured prostate cancer cells and tumors in mice, and this effect can be overcome by the AKT inhibitor. Our findings reveal BET proteins as proteolytic targets of SPOP and identify deregulated cholesterol biosynthesis as a downstream event of SPOP mutation-mediated tumorigenesis and therapy resistance in prostate cancer.
Overall design Examination of BRD4 binding in SPOP wt and mutation stable cell lines with JQ1 treatment or in the BRD4 overexpression cells.
Contributor(s) Zhao Y, Ye Z, Liguo W, Huang H
Citation(s) 28805822
Submission date Oct 18, 2016
Last update date May 15, 2019
Contact name Zhenqing Ye
Organization name Mayo Clinic
Department Biomedical Statistics and Informatics
Street address 200 First St. SW
City Rochester
State/province MN
ZIP/Postal code 55905
Country USA
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (10)
GSM2350445 EV_DMSO rep1
GSM2350446 EV_JQ1 rep1
GSM2350447 F133V_DMSO rep1
This SubSeries is part of SuperSeries:
GSE88872 SPOP mutation confers intrinsic BET inhibitor resistance in prostate cancer
BioProject PRJNA349004
SRA SRP091739

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Supplementary file Size Download File type/resource
GSE88871_RAW.tar 2.1 Gb (http)(custom) TAR (of BIGWIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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