Complementary whole-genome technologies reveal the cellular response to proteasome inhibition by PS-341
| Autor: | Christine E. Bulawa, Ronald K. Blackman, Seth Sadis, Vala Thoroddsen, Eric S. Lightcap, James Fleming |
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| Rok vydání: | 2002 |
| Předmět: |
Proteasome Endopeptidase Complex
DNA Repair Transcription Genetic Saccharomyces cerevisiae Microbial Sensitivity Tests Protein degradation Bortezomib Fungal Proteins Multienzyme Complexes medicine Protease Inhibitors DNA Fungal Gene Transcription factor Oligonucleotide Array Sequence Analysis Cell Nucleus Fungal protein Multidisciplinary biology Gene Expression Profiling RNA Fungal Genomics Biological Sciences biology.organism_classification Boronic Acids Cell biology Gene expression profiling Cysteine Endopeptidases Biochemistry Pyrazines Proteasome inhibitor Genome Fungal Gene Deletion Function (biology) medicine.drug |
| Zdroj: | Proceedings of the National Academy of Sciences. 99:1461-1466 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.032516399 |
| Popis: | Although the biochemical targets of most drugs are known, the biological consequences of their actions are typically less well understood. In this study, we have used two whole-genome technologies in Saccharomyces cerevisiae to determine the cellular impact of the proteasome inhibitor PS-341. By combining population genomics, the screening of a comprehensive panel of bar-coded mutant strains, and transcript profiling, we have identified the genes and pathways most affected by proteasome inhibition. Many of these function in regulated protein degradation or a subset of mitotic activities. In addition, we identified Rpn4p as the transcription factor most responsible for the cell's ability to compensate for proteasome inhibition. Used together, these complementary technologies provide a general and powerful means to elucidate the cellular ramifications of drug treatment. |
| Databáze: | OpenAIRE |
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