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 ArticleDOI
The BioGRID Interaction Database: 2008 update
Bobby-Joe Breitkreutz,Chris Stark,Teresa Reguly,Lorrie Boucher,Ashton Breitkreutz,Michael S. Livstone,Rose Oughtred,Daniel H. Lackner,Jürg Bähler,Valerie Wood,Kara Dolinski,Mike Tyers +11 more
TL;DR: A number of new features have been added to the BioGRID including an improved user interface to display interactions based on different attributes, a mirror site and a dedicated interaction management system to coordinate curation across different locations.
Journal ArticleDOI
Proteome-wide Analysis of Chaperonin-Dependent Protein Folding in Escherichia coli
Michael J. Kerner,Dean J. Naylor,Yasushi Ishihama,Tobias Maier,Hung-Chun Chang,Anna P. Stines,Costa Georgopoulos,Dmitrij Frishman,Manajit Hayer-Hartl,Matthias Mann,F. Ulrich Hartl +10 more
TL;DR: It is suggested that the chaperonin system may have facilitated the evolution of this fold into a versatile platform for the implementation of numerous enzymatic functions.
Journal ArticleDOI
Hsp90 potentiates the rapid evolution of new traits: drug resistance in diverse fungi.
Leah E. Cowen,Susan Lindquist +1 more
TL;DR: Hsp90 can act in diverse ways to couple environmental contingency to the emergence and fixation of new traits, and during selection in a human host, drug resistance that was initially Hsp90-dependent evolved toward independence.
Journal ArticleDOI
Hsp90 Cochaperone Aha1 Downregulation Rescues Misfolding of CFTR in Cystic Fibrosis
Xiaodong Wang,John D. Venable,Paul LaPointe,Darren M. Hutt,Atanas V. Koulov,Judith A. Coppinger,Cemal Gurkan,Wendy Kellner,Jeanne Matteson,Helen Plutner,John R. Riordan,Jeffery W. Kelly,John R. Yates,William E. Balch +13 more
TL;DR: It is proposed that failure of DeltaF508 to achieve an energetically favorable fold in response to the steady-state dynamics of the chaperone folding environment (the "chaperome") is responsible for the pathophysiology of CF.
Journal ArticleDOI
PINK1 Protects against Oxidative Stress by Phosphorylating Mitochondrial Chaperone TRAP1
TL;DR: The identification of TNF receptor-associated protein 1 (TRAP1), a mitochondrial molecular chaperone also known as heat shock protein 75 (Hsp75), as a cellular substrate for PINK1 kinase is reported, and a novel pathway by which Pink1 phosphorylates downstream effector TRAP1 to prevent oxidative-stress-induced apoptosis is suggested.