Heat-Shock Protein 90 Controls the Expression of Cell-Cycle Genes by Stabilizing Metazoan-Specific Host-Cell Factor HCFC1.
Animals
Cell Line, Tumor
Cell Nucleus
/ metabolism
Cell Proliferation
/ genetics
Chromatin
/ metabolism
Chromatin Immunoprecipitation Sequencing
Cyclin-Dependent Kinase 9
/ antagonists & inhibitors
Cytosol
/ metabolism
Databases, Genetic
Gene Expression Regulation, Neoplastic
/ genetics
Genes, cdc
HSP90 Heat-Shock Proteins
/ antagonists & inhibitors
Host Cell Factor C1
/ genetics
Humans
Mice
Protein Binding
Protein Interaction Maps
RNA-Seq
HCFC1
HSP90
cancer
chaperone
chromatin
synergistic inhibition
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
05 11 2019
05 11 2019
Historique:
received:
19
03
2019
revised:
06
08
2019
accepted:
27
09
2019
entrez:
7
11
2019
pubmed:
7
11
2019
medline:
25
9
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31693902
pii: S2211-1247(19)31288-4
doi: 10.1016/j.celrep.2019.09.084
pii:
doi:
Substances chimiques
Chromatin
0
HSP90 Heat-Shock Proteins
0
Host Cell Factor C1
0
CDK9 protein, human
EC 2.7.11.22
Cyclin-Dependent Kinase 9
EC 2.7.11.22
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1645-1659.e9Subventions
Organisme : Medical Research Council
ID : MC_UU_00025/8
Pays : United Kingdom
Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.