Journal ArticleDOI
HSP90 at the hub of protein homeostasis: emerging mechanistic insights
TLDR
Comprehensive understanding of how HSP90 functions promises not only to provide new avenues for therapeutic intervention, but to shed light on fundamental biological questions.Abstract:
Heat shock protein 90 (HSP90) is a highly conserved molecular chaperone that facilitates the maturation of a wide range of proteins (known as clients). Clients are enriched in signal transducers, including kinases and transcription factors. Therefore, HSP90 regulates diverse cellular functions and exerts marked effects on normal biology, disease and evolutionary processes. Recent structural and functional analyses have provided new insights on the transcriptional and biochemical regulation of HSP90 and the structural dynamics it uses to act on a diverse client repertoire. Comprehensive understanding of how HSP90 functions promises not only to provide new avenues for therapeutic intervention, but to shed light on fundamental biological questions.read more
Citations
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Journal ArticleDOI
Molecular chaperones in protein folding and proteostasis
TL;DR: It is suggested that an age-related decline in proteostasis capacity allows the manifestation of various protein-aggregation diseases, including Alzheimer's disease and Parkinson's disease, which may spring from a detailed understanding of the pathways underlying proteome maintenance.
Journal ArticleDOI
The Heat Shock Response: Life on the Verge of Death
TL;DR: This Review summarizes the concepts of the protective Hsp network, and the most conserved Hsps are molecular chaperones that prevent the formation of nonspecific protein aggregates and assist proteins in the acquisition of their native structures.
Journal ArticleDOI
Combining immunotherapy and targeted therapies in cancer treatment
TL;DR: Targeted therapies and cytotoxic agents also modulate immune responses, which raises the possibility that these treatment strategies might be effectively combined with immunotherapy to improve clinical outcomes.
Journal ArticleDOI
Molecular Chaperone Functions in Protein Folding and Proteostasis
TL;DR: This review focuses on recent advances in understanding the mechanisms of chaperone action in promoting and regulating protein folding and on the pathological consequences of protein misfolding and aggregation.
Journal ArticleDOI
In vivo aspects of protein folding and quality control
TL;DR: A new view of protein folding is emerging, whereby the energy landscapes that proteins navigate during folding in vivo may differ substantially from those observed during refolding in vitro.
References
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Journal Article
Evidence for reversible, non-microtubule and non-microfilament-dependent nuclear translocation of hsp90 after heat shock in human fibroblasts
TL;DR: A monoclonal antibody directed against rat liver heat shock protein M(r) 90,000 (hsp90) was produced and a major part of hsp90 immunoreactivity was diffusely distributed throughout the interphase cytoplasm, but a weak nuclear staining with non-stained nucleoli was also present, however, only detectable after methanol and not after formaldehyde/Triton X-100 fixation.
Journal ArticleDOI
Defining the requirements for Hsp40 and Hsp70 in the Hsp90 chaperone pathway
Nela S. Cintron,David O. Toft +1 more
TL;DR: Mutation studies indicate that client binding, interactions between Hsp40 and Hsp70, plus ATP hydrolysis by HSp70 are all required to promote conformational maturation of PR via the Hsp90 pathway.
Journal ArticleDOI
GERp95 belongs to a family of signal-transducing proteins and requires Hsp90 activity for stability and Golgi localization.
TL;DR: Results indicate that GERp95 engages an Hsp90 chaperone complex prior to association with intracellular membranes and is associated with the Golgi in normal rat kidney cells.
Journal ArticleDOI
The activity of hsp90 alpha promoter is regulated by NF-kappa B transcription factors.
Massimo Ammirante,Alessandra Rosati,Antonio Gentilella,Michelina Festa,Antonello Petrella,Liberato Marzullo,Maria Pascale,Maria Antonietta Belisario,Arturo Leone,Maria Caterina Turco +9 more
TL;DR: It is found that NF-κB factors bound to one of the two putative consensus sequences present in the hsp90α-flanking region; mutation of such motif hampered the phorbol-myristate-13-acetate-stimulated expression of a luciferase reporter gene under the control of the hSP90α promoter.
Journal ArticleDOI
Hsp90 increases LIM kinase activity by promoting its homo-dimerization
Rong Li,Juliana Soosairajah,Daniel Harari,Ami Citri,John T. Price,Hooi Ling Ng,Craig J. Morton,Michael W. Parker,Yosef Yarden,Ora Bernard +9 more
TL;DR: It is shown that the half‐life of LIMK1 in cells depends on the presence of active Hsp90, and these findings implicate HSp90 in the stabilization of LimK1 by promoting homodimer formation and transphosphorylation.