Hsp70 molecular chaperones: Emerging roles in human disease and identification of small molecule modulators Journal Article


Authors: Brodsky, J. L.; Chiosis, G.
Article Title: Hsp70 molecular chaperones: Emerging roles in human disease and identification of small molecule modulators
Abstract: Molecular chaperones are best known for their ability to aid in the solubilization of mis-folded proteins, and as a result play essential roles in protein folding, degradation, and transport. However, many molecular chaperones also play essential roles in signal transduction cascades. For example, Hsp70 molecular chaperones are a highly conserved, abundant class of chaperones that are found in every species and in nearly every cellular compartment in eukaryotes. In addition to their well-established roles in facilitating protein folding and in the targeting of proteins to organelles and to proteolytic machines, Hsp70s are anti-apoptotic and inhibition of Hsp70 function in some cases is sufficient to induce tumor cell death. Hsp70 function is also vital for the replication of viruses. Based on these data, small molecule Hsp70 modulators might, in principle, be used for the treatment of specific cancers, infections, and protein conformational diseases. In this review, we summarize the structural and functional characteristics of Hsp70 chaperones, and then discuss their roles in cellular physiology. Finally, we will review the recent discovery of small molecules that alter Hsp70 expression and function. © 2006 Bentham Science Publishers Ltd.
Keywords: signal transduction; protein expression; unclassified drug; clinical trial; review; nonhuman; unspecified side effect; antineoplastic agent; ubiquitin; protein conformation; protein function; cell death; cell function; apoptosis; bortezomib; proteasome; infection; multiple myeloma; benzyloxycarbonylleucylleucylleucinal; protein degradation; protein targeting; inflammation; drug design; cancer therapy; ischemia; transmembrane conductance regulator; protein transport; tumor cell; simian virus 40; heat shock protein 90; hsp90 heat-shock proteins; heat shock protein 70; virus replication; protein folding; protein structure; parkinson disease; natural product; cell organelle; alzheimer disease; kidney graft rejection; chaperone; disease; molecular chaperones; huntington chorea; motor neuron disease; 17 allylamino 17 demethoxygeldanamycin; tumor immunogenicity; apoptosis signaling; hsp90 chaperone; proteasome pathway; stress-activated jun n-terminal kinase; 15 deoxyspergualin; celastrol; galactolipid; lactacystin; nsc 630668; teprenone; solubilization
Journal Title: Current Topics in Medicinal Chemistry
Volume: 6
Issue: 11
ISSN: 1568-0266
Publisher: Bentham Science Publishers  
Date Published: 2006-06-01
Start Page: 1215
End Page: 1225
Language: English
DOI: 10.2174/156802606777811997
PUBMED: 16842158
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 80" - "Export Date: 4 June 2012" - "CODEN: CTMCC" - "Source: Scopus"
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  1. Gabriela Chiosis
    216 Chiosis