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| Status |
Public on Oct 17, 2013 |
| Title |
Global response to chemotherapy-induced apoptosis |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| 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.
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| 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.
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| 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
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| Department |
Laboratory Medicine
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| Street address |
185 Berry St., Suite 290
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| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94107 |
| Country |
USA |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (12)
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| GSM1184594 |
1.5h_MM1S_20nM_bortezomib_ribosome_footprint |
| GSM1184595 |
3h_MM1S_20nM_bortezomib_polyA_mRNA |
| GSM1184596 |
3h_MM1S_20nM_bortezomib_ribosome_footprint |
| GSM1184597 |
6h_MM1S_20nM_bortezomib_polyA_mRNA |
| GSM1184598 |
6h_MM1S_20nM_bortezomib_ribosome_footprint |
| GSM1184599 |
9h_MM1S_20nM_bortezomib_polyA_mRNA |
| GSM1184600 |
9h_MM1S_20nM_bortezomib_ribosome_footprint |
| GSM1184601 |
12h_MM1S_20nM_bortezomib_polyA_mRNA |
| GSM1184602 |
12h_MM1S_20nM_bortezomib_ribosome_footprint |
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| Relations |
| BioProject |
PRJNA211752 |
| SRA |
SRP027015 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE48785_Sequencing_counts.xlsx.gz |
1.6 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Processed data are available on Series record |
| Raw data are available in SRA |
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