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Series GSE48785 Query DataSets for GSE48785
Status Public on Oct 17, 2013
Title Global response to chemotherapy-induced apoptosis
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Here we use an integrated systems-level examination of transcription, translation, and proteolysis to explore how cancer cells struggle with a chemotherapeutic drug prior to succumbing to apoptosis. As a model system we study myeloma cells exposed to the proteasome inhibitor bortezomib, a first-line clinical treatment. Despite robust transcriptional changes, unbiased quantitative proteomics detects production of only a few critical anti-apoptotic proteins against a background of general translation inhibition. Ribosome profiling further reveals potential translational regulation of stress response genes following bortezomib treatment. Once the apoptotic machinery is engaged, degradation by caspases is largely independent of changes at the transcriptional level. Moreover, previously uncharacterized non-caspase proteolytic events also participate in cellular deconstruction. As suggested by these data, we find that inhibition of the anti-apoptotic response regulator HSF1 promotes cell death by bortezomib. Thus, monitoring global cellular dynamics after chemotherapy offers in-depth insight into apoptosis and can also guide potential therapeutic combinations.
Overall design We examined MM1.S myeloma cells exposed to 20 nM bortezomib across a time course with independent samples of poly(A) mRNA and ribosome footprints isolated at each of six time points (0h (untreated), 1.5h, 3h, 6h, 9h, 12h). Sequencing was performed on a Illumina HiSeq 2000 with single-end.
Contributor(s) Wiita AP, Ziv E, Wiita PJ, Urisman A, Julien O, Burlingame AL, Weissman JS, Wells JA
Citation(s) 24171104
Submission date Jul 11, 2013
Last update date May 15, 2019
Contact name Arun P. Wiita
Organization name University of California, San Francisco
Department Laboratory Medicine
Street address 185 Berry St., Suite 290
City San Francisco
State/province CA
ZIP/Postal code 94107
Country USA
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (12)
GSM1184591 0h_MM1S_untreated_polyA_mRNA
GSM1184592 0h_MM1S_untreated_ribosome_footprint
GSM1184593 1.5h_MM1S_20nM_bortezomib_polyA_mRNA
BioProject PRJNA211752
SRA SRP027015

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Supplementary file Size Download File type/resource
GSE48785_Sequencing_counts.xlsx.gz 1.6 Mb (ftp)(http) XLSX
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Raw data are available in SRA

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