Global analysis of genome, transcriptome and proteome reveals the response to aneuploidy in human cells
Abstract Extra chromosome copies markedly alter the physiology of eukaryotic cells, but the underlying reasons are not well understood. We created human trisomic and tetrasomic cell lines and determined the quantitative changes in their transcriptome and proteome in comparison with their diploid cou...
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| Format: | Article |
| Language: | English |
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Springer Nature
2012-09-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.1038/msb.2012.40 |
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| author | Silvia Stingele Gabriele Stoehr Karolina Peplowska Jürgen Cox Matthias Mann Zuzana Storchova |
| author_facet | Silvia Stingele Gabriele Stoehr Karolina Peplowska Jürgen Cox Matthias Mann Zuzana Storchova |
| author_sort | Silvia Stingele |
| collection | DOAJ |
| description | Abstract Extra chromosome copies markedly alter the physiology of eukaryotic cells, but the underlying reasons are not well understood. We created human trisomic and tetrasomic cell lines and determined the quantitative changes in their transcriptome and proteome in comparison with their diploid counterparts. We found that whereas transcription levels reflect the chromosome copy number changes, the abundance of some proteins, such as subunits of protein complexes and protein kinases, is reduced toward diploid levels. Furthermore, using the quantitative data we investigated the changes of cellular pathways in response to aneuploidy. This analysis revealed specific and uniform alterations in pathway regulation in cells with extra chromosomes. For example, the DNA and RNA metabolism pathways were downregulated, whereas several pathways such as energy metabolism, membrane metabolism and lysosomal pathways were upregulated. In particular, we found that the p62‐dependent selective autophagy is activated in the human trisomic and tetrasomic cells. Our data present the first broad proteomic analysis of human cells with abnormal karyotypes and suggest a uniform cellular response to the presence of an extra chromosome. |
| format | Article |
| id | doaj-art-7a2a4fc720c34ba89b5430c5e4b85656 |
| institution | OA Journals |
| issn | 1744-4292 |
| language | English |
| publishDate | 2012-09-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-7a2a4fc720c34ba89b5430c5e4b856562025-08-20T02:18:32ZengSpringer NatureMolecular Systems Biology1744-42922012-09-018111210.1038/msb.2012.40Global analysis of genome, transcriptome and proteome reveals the response to aneuploidy in human cellsSilvia Stingele0Gabriele Stoehr1Karolina Peplowska2Jürgen Cox3Matthias Mann4Zuzana Storchova5Group of Maintenance of Genome Stability, Max Planck Institute of BiochemistryDepartment of Proteomics and Signal Transduction, Max Planck Institute of BiochemistryGroup of Maintenance of Genome Stability, Max Planck Institute of BiochemistryDepartment of Proteomics and Signal Transduction, Max Planck Institute of BiochemistryDepartment of Proteomics and Signal Transduction, Max Planck Institute of BiochemistryGroup of Maintenance of Genome Stability, Max Planck Institute of BiochemistryAbstract Extra chromosome copies markedly alter the physiology of eukaryotic cells, but the underlying reasons are not well understood. We created human trisomic and tetrasomic cell lines and determined the quantitative changes in their transcriptome and proteome in comparison with their diploid counterparts. We found that whereas transcription levels reflect the chromosome copy number changes, the abundance of some proteins, such as subunits of protein complexes and protein kinases, is reduced toward diploid levels. Furthermore, using the quantitative data we investigated the changes of cellular pathways in response to aneuploidy. This analysis revealed specific and uniform alterations in pathway regulation in cells with extra chromosomes. For example, the DNA and RNA metabolism pathways were downregulated, whereas several pathways such as energy metabolism, membrane metabolism and lysosomal pathways were upregulated. In particular, we found that the p62‐dependent selective autophagy is activated in the human trisomic and tetrasomic cells. Our data present the first broad proteomic analysis of human cells with abnormal karyotypes and suggest a uniform cellular response to the presence of an extra chromosome.https://doi.org/10.1038/msb.2012.40aneuploidyautophagypathway analysisproteomicsp62 |
| spellingShingle | Silvia Stingele Gabriele Stoehr Karolina Peplowska Jürgen Cox Matthias Mann Zuzana Storchova Global analysis of genome, transcriptome and proteome reveals the response to aneuploidy in human cells Molecular Systems Biology aneuploidy autophagy pathway analysis proteomics p62 |
| title | Global analysis of genome, transcriptome and proteome reveals the response to aneuploidy in human cells |
| title_full | Global analysis of genome, transcriptome and proteome reveals the response to aneuploidy in human cells |
| title_fullStr | Global analysis of genome, transcriptome and proteome reveals the response to aneuploidy in human cells |
| title_full_unstemmed | Global analysis of genome, transcriptome and proteome reveals the response to aneuploidy in human cells |
| title_short | Global analysis of genome, transcriptome and proteome reveals the response to aneuploidy in human cells |
| title_sort | global analysis of genome transcriptome and proteome reveals the response to aneuploidy in human cells |
| topic | aneuploidy autophagy pathway analysis proteomics p62 |
| url | https://doi.org/10.1038/msb.2012.40 |
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