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Heat-Shock Protein 90 Controls the Expression of Cell-Cycle Genes by Stabilizing Metazoan-Specific Host-Cell Factor HCFC1
- Source :
- Cell Reports, Vol 29, Iss 6, Pp 1645-1659.e9 (2019)
- Publication Year :
- 2019
- Publisher :
- Elsevier, 2019.
-
Abstract
- 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
- Subjects :
- Biology (General)
QH301-705.5
Subjects
Details
- Language :
- English
- ISSN :
- 22111247
- Volume :
- 29
- Issue :
- 6
- Database :
- Directory of Open Access Journals
- Journal :
- Cell Reports
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.b0e8519e759d44d6bd040867ed687809
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.celrep.2019.09.084