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
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Phosphorylation of the outer membrane mitochondrial protein OM64 influences protein import into mitochondria
Catharina Nickel,Regina Horneff,Ralf Heermann,Boris Neumann,Kirsten Jung,Jürgen Soll,Serena Schwenkert +6 more
TL;DR: In vivo expression of genes encoding different OM64 variants in planta revealed that phosphorylation of OM64 impairs the import efficiency of the mitochondrial preprotein pFAD, a subunits of the Mitochondrial ATP synthase.
Journal ArticleDOI
Visualising dual downregulation of insulin-like growth factor receptor-1 and vascular endothelial growth factor-A by heat shock protein 90 inhibition effect in triple negative breast cancer
Anton G.T. Terwisscha van Scheltinga,Paul Berghuis,Hilde H. Nienhuis,Hetty Timmer-Bosscha,Linda Pot,Sietske B. M. Gaykema,Marjolijn N. Lub-de Hooge,Jos G. W. Kosterink,Elisabeth G.E. de Vries,Carolien P. Schröder +9 more
TL;DR: In vivo PET imaging can reflect effect of Hsp90 inhibitors and can therefore potentially be used to monitor therapeutic effects of HSp90 inhibitor therapy in TNBC.
Journal ArticleDOI
Oral Hsp90 inhibitor SNX-5422 attenuates SARS-CoV-2 replication and dampens inflammation in airway cells.
Ria Goswami,Veronica S. Russell,Joshua J. Tu,Charlene Thomas,Philip F. Hughes,Francine Kelly,Stephanie N. Langel,Justin Steppe,Scott M. Palmer,Timothy A.J. Haystead,Maria Blasi,Sallie R. Permar +11 more
TL;DR: In this article, an orally bioavailable Hsp90 inhibitor, SNX-5422, currently in clinical trials as an anti-cancer therapeutic, inhibits SARS-CoV-2 replication in vitro at a high selectivity index.
Journal ArticleDOI
Chaperone Proteins Select and Maintain [PIN+] Prion Conformations in Saccharomyces cerevisiae
TL;DR: It is shown that deletion of specific chaperone genes alters [PIN+] variant phenotypes, including [PSI+] induction efficiency, Rnq1p aggregate morphology/size and variant dominance, which demonstrate a role for chaperones in regulating the prion variant complement of a cell.
Journal ArticleDOI
Dendritic cells sequester antigenic epitopes for prolonged periods in the absence of antigen-encoding genetic information.
Changying Li,Changying Li,Matthew R. Buckwalter,Sreyashi Basu,Manish Garg,Jiwu Chang,Pramod K. Srivastava +6 more
TL;DR: It is demonstrated that epitopes, or epitope precursors, of a model antigen (ovalbumin) persist in a host for prolonged periods (weeks), well beyond the time at which the intact antigen has disappeared, and in the complete absence of genetic information encoding it.
References
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