| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 29, Iss 6, Pp 1645-1659.e9 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2019.09.084 |
| Popis: |
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 |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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