PMID: 8962087Dec 10, 1996Paper

Pharmacologic shifting of a balance between protein refolding and degradation mediated by Hsp90

Proceedings of the National Academy of Sciences of the United States of America
C SchneiderF Ulrich Hartl

Abstract

The role of the abundant stress protein Hsp90 in protecting cells against stress-induced damage is not well understood. The recent discovery that a class of ansamycin antibiotics bind specifically to Hsp90 allowed us to address this problem from a new angle. We find that mammalian Hsp90, in cooperation with Hsp70, p60, and other factors, mediates the ATP-dependent refolding of heat-denatured proteins, such as firefly luciferase. Failure to refold results in proteolysis. The ansamycins inhibit refolding, both in vivo and in a cell extract, by preventing normal dissociation of Hsp90 from luciferase, causing its enhanced degradation. This mechanism also explains the ansamycin-induced proteolysis of several protooncogenic protein kinases, such as Raf-1, which interact with Hsp90. We propose that Hsp90 is part of a quality control system that facilitates protein refolding or degradation during recovery from stress. This function is used by a limited set of signal transduction molecules for their folding and regulation under nonstress conditions. The ansamycins shift the mode of Hsp90 from refolding to degradation, and this effect is probably amplified for specific Hsp90 substrates.

References

Jan 1, 1992·Annual Review of Genetics·S Jentsch
Jul 9, 1992·Nature·H WiechU Jakob
Apr 1, 1991·Trends in Biochemical Sciences·E A Craig, C A Gross
Sep 1, 1989·Molecular and Cellular Biology·C M Nicolet, E A Craig
May 16, 1985·Biochemical and Biophysical Research Communications·A Hershko, H Heller
Nov 15, 1985·Biochemical and Biophysical Research Communications·Y HirataT Fujita
Nov 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·A L Haas, I A Rose
Oct 1, 1995·Journal of Cellular Physiology·R S HegdeW J Welch
Jul 14, 1995·The Journal of Biological Chemistry·L Sepp-LorenzinoN Rosen
Feb 15, 1994·European Journal of Biochemistry·V T Nguyen, O Bensaude
May 1, 1994·Trends in Biochemical Sciences·U Jakob, J Buchner
Apr 1, 1994·Seminars in Cell Biology·W B Pratt, M J Welsh
Aug 30, 1994·Proceedings of the National Academy of Sciences of the United States of America·L WhitesellL M Neckers
Feb 2, 1996·The Journal of Biological Chemistry·M YoneharaI Yahara

❮ Previous
Next ❯

Citations

Oct 20, 1998·Annals of Neurology·F R Sharp
Nov 9, 2004·Chembiochem : a European Journal of Chemical Biology·John S Schneekloth, Craig M Crews
Dec 10, 2002·International Journal of Cancer. Journal International Du Cancer·Sunghoon KimDai H Chung
Nov 20, 2002·The Journal of Gene Medicine·Christopher J MannStephen D Wilton
Dec 11, 2002·The Journal of Pathology·P J Coates, P A Hall
Jul 24, 2010·Cancer Chemotherapy and Pharmacology·Howard A BurrisSuzanne Jones
May 31, 2007·Journal of Biosciences·Len Neckers
Apr 4, 2008·Cell Stress & Chaperones·Pascale FlandrinLydia Campos
Jun 30, 2009·Cellular Immunology·Shuping FangZhimin Yin
May 3, 2005·The Journal of Steroid Biochemistry and Molecular Biology·Despina SirianiMichael N Alexis
Jun 21, 2002·Biochemical and Biophysical Research Communications·Stéphane ManentiJean-Marie Darbon
Mar 29, 2002·Neurochemistry International·Hye-Young YoonSoo Young Choi
Jun 24, 2000·Bioorganic & Medicinal Chemistry Letters·S D KudukS J Danishefsky
May 26, 1999·Bioorganic & Medicinal Chemistry Letters·S D KudukS J Danishefsky
May 14, 1999·Trends in Biochemical Sciences·J Buchner
Apr 15, 2008·Trends in Endocrinology and Metabolism : TEM·D O Toft
Oct 5, 2001·Molecular Cell·C M Pickart
Apr 3, 2002·Trends in Molecular Medicine·Len Neckers
Apr 5, 2003·Cancer Cell·Jennifer S IsaacsLen Neckers
Jan 8, 2013·Journal of the American Chemical Society·Yi-Ping ChenChung-Yuan Mou
Nov 18, 2008·Nature Cell Biology·Taner DoganKrishnaraj Rajalingam
Oct 8, 2005·Nature Medicine·Albert R La Spada, Patrick Weydt
Sep 6, 2011·Nature Methods·Rajat GuptaSwasti Raychaudhuri
Jun 1, 1997·Nature Structural Biology·A Joachimiak
Apr 12, 2001·European Journal of Biochemistry·M MinamiY Minami
Jan 25, 2008·Proceedings of the National Academy of Sciences of the United States of America·Margaret K CallahanPramod K Srivastava
Oct 24, 2012·The Journal of Biological Chemistry·Imad BaakliniJason C Young
Dec 15, 2011·Molecular & Cellular Proteomics : MCP·Kirti SharmaF Ulrich Hartl
Oct 17, 2013·Assay and Drug Development Technologies·Takrima SadikotGeorge A Vielhauer
Nov 5, 1998·Molecular Biology of the Cell·J F LouvionD Picard

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.