Heat-Shock Protein 90 Controls the Expression of Cell-Cycle Genes by Stabilizing Metazoan-Specific Host-Cell Factor HCFC1
Summary: Molecular chaperones such as heat-shock proteins (HSPs) help in protein folding. Their function in the cytosol has been well studied. Notably, chaperones are also present in the nucleus, a compartment where proteins enter after completing de novo folding in the cytosol, and this raises an i...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-11-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719312884 |
| _version_ | 1819236922123354112 |
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| author | Aneliya Antonova Barbara Hummel Ashkan Khavaran Desiree M. Redhaber Fernando Aprile-Garcia Prashant Rawat Kathrin Gundel Megan Schneck Erik C. Hansen Jan Mitschke Gerhard Mittler Cornelius Miething Ritwick Sawarkar |
| author_facet | Aneliya Antonova Barbara Hummel Ashkan Khavaran Desiree M. Redhaber Fernando Aprile-Garcia Prashant Rawat Kathrin Gundel Megan Schneck Erik C. Hansen Jan Mitschke Gerhard Mittler Cornelius Miething Ritwick Sawarkar |
| author_sort | Aneliya Antonova |
| collection | DOAJ |
| description | Summary: Molecular chaperones such as heat-shock proteins (HSPs) help in protein folding. Their function in the cytosol has been well studied. Notably, chaperones are also present in the nucleus, a compartment where proteins enter after completing de novo folding in the cytosol, and this raises an important question about chaperone function in the nucleus. We performed a systematic analysis of the nuclear pool of heat-shock protein 90. Three orthogonal and independent analyses led us to the core functional interactome of HSP90. Computational and biochemical analyses identify host cell factor C1 (HCFC1) as a transcriptional regulator that depends on HSP90 for its stability. HSP90 was required to maintain the expression of HCFC1-targeted cell-cycle genes. The regulatory nexus between HSP90 and the HCFC1 module identified in this study sheds light on the relevance of chaperones in the transcription of cell-cycle genes. Our study also suggests a therapeutic avenue of combining chaperone and transcription inhibitors for cancer treatment. : What do chaperones do in the nucleus? Antonova et al. perform a comprehensive genetic and physical interactome analysis of nuclear HSP90 in human cells. HSP90 stabilizes the HCFC1 complex at chromatin, contributing to the expression of HCFC1-targeted cell-cycle genes. The simultaneous inhibition of HSP90 and transcription is synergistic in killing cancer cells. Keywords: chaperone, HSP90, HCFC1, chromatin, cancer, synergistic inhibition |
| first_indexed | 2024-12-23T13:12:08Z |
| format | Article |
| id | doaj.art-b0e8519e759d44d6bd040867ed687809 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-23T13:12:08Z |
| publishDate | 2019-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-b0e8519e759d44d6bd040867ed6878092022-12-21T17:45:42ZengElsevierCell Reports2211-12472019-11-0129616451659.e9Heat-Shock Protein 90 Controls the Expression of Cell-Cycle Genes by Stabilizing Metazoan-Specific Host-Cell Factor HCFC1Aneliya Antonova0Barbara Hummel1Ashkan Khavaran2Desiree M. Redhaber3Fernando Aprile-Garcia4Prashant Rawat5Kathrin Gundel6Megan Schneck7Erik C. Hansen8Jan Mitschke9Gerhard Mittler10Cornelius Miething11Ritwick Sawarkar12Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany; Faculty of Biology, University of Freiburg, Freiburg, GermanyMax Planck Institute of Immunobiology and Epigenetics, Freiburg, GermanyMax Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, GermanyGerman Consortium for Translational Cancer Research (DKTK), Partner Site Freiburg and German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Hematology, Oncology and Stem Cell Transplantation, Faculty of Medicine, Medical Center - University of Freiburg, Freiburg, Germany; Faculty of Biology, University of Freiburg, Freiburg, GermanyMax Planck Institute of Immunobiology and Epigenetics, Freiburg, GermanyMax Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany; Faculty of Biology, University of Freiburg, Freiburg, GermanyMax Planck Institute of Immunobiology and Epigenetics, Freiburg, GermanyMax Planck Institute of Immunobiology and Epigenetics, Freiburg, GermanyMax Planck Institute of Immunobiology and Epigenetics, Freiburg, GermanyDepartment of Hematology, Oncology and Stem Cell Transplantation, Faculty of Medicine, Medical Center - University of Freiburg, Freiburg, GermanyMax Planck Institute of Immunobiology and Epigenetics, Freiburg, GermanyGerman Consortium for Translational Cancer Research (DKTK), Partner Site Freiburg and German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Hematology, Oncology and Stem Cell Transplantation, Faculty of Medicine, Medical Center - University of Freiburg, Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg, GermanyMax Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany; CIBSS Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany; MRC Toxicology Unit, University of Cambridge, Cambridge, UK; Corresponding authorSummary: Molecular chaperones such as heat-shock proteins (HSPs) help in protein folding. Their function in the cytosol has been well studied. Notably, chaperones are also present in the nucleus, a compartment where proteins enter after completing de novo folding in the cytosol, and this raises an important question about chaperone function in the nucleus. We performed a systematic analysis of the nuclear pool of heat-shock protein 90. Three orthogonal and independent analyses led us to the core functional interactome of HSP90. Computational and biochemical analyses identify host cell factor C1 (HCFC1) as a transcriptional regulator that depends on HSP90 for its stability. HSP90 was required to maintain the expression of HCFC1-targeted cell-cycle genes. The regulatory nexus between HSP90 and the HCFC1 module identified in this study sheds light on the relevance of chaperones in the transcription of cell-cycle genes. Our study also suggests a therapeutic avenue of combining chaperone and transcription inhibitors for cancer treatment. : What do chaperones do in the nucleus? Antonova et al. perform a comprehensive genetic and physical interactome analysis of nuclear HSP90 in human cells. HSP90 stabilizes the HCFC1 complex at chromatin, contributing to the expression of HCFC1-targeted cell-cycle genes. The simultaneous inhibition of HSP90 and transcription is synergistic in killing cancer cells. Keywords: chaperone, HSP90, HCFC1, chromatin, cancer, synergistic inhibitionhttp://www.sciencedirect.com/science/article/pii/S2211124719312884 |
| spellingShingle | Aneliya Antonova Barbara Hummel Ashkan Khavaran Desiree M. Redhaber Fernando Aprile-Garcia Prashant Rawat Kathrin Gundel Megan Schneck Erik C. Hansen Jan Mitschke Gerhard Mittler Cornelius Miething Ritwick Sawarkar Heat-Shock Protein 90 Controls the Expression of Cell-Cycle Genes by Stabilizing Metazoan-Specific Host-Cell Factor HCFC1 Cell Reports |
| title | Heat-Shock Protein 90 Controls the Expression of Cell-Cycle Genes by Stabilizing Metazoan-Specific Host-Cell Factor HCFC1 |
| title_full | Heat-Shock Protein 90 Controls the Expression of Cell-Cycle Genes by Stabilizing Metazoan-Specific Host-Cell Factor HCFC1 |
| title_fullStr | Heat-Shock Protein 90 Controls the Expression of Cell-Cycle Genes by Stabilizing Metazoan-Specific Host-Cell Factor HCFC1 |
| title_full_unstemmed | Heat-Shock Protein 90 Controls the Expression of Cell-Cycle Genes by Stabilizing Metazoan-Specific Host-Cell Factor HCFC1 |
| title_short | Heat-Shock Protein 90 Controls the Expression of Cell-Cycle Genes by Stabilizing Metazoan-Specific Host-Cell Factor HCFC1 |
| title_sort | heat shock protein 90 controls the expression of cell cycle genes by stabilizing metazoan specific host cell factor hcfc1 |
| url | http://www.sciencedirect.com/science/article/pii/S2211124719312884 |
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