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.
Keywords: Hsp90 chaperone, apoptosis signaling, stress-activated Jun N-terminal kinase, Proteasome Pathway, Tumor Immunogenicity
Current Topics in Medicinal Chemistry
Title: Hsp70 Molecular Chaperones: Emerging Roles in Human Disease and Identification of Small Molecule Modulators
Volume: 6 Issue: 11
Author(s): Jeffrey L. Brodsky and Gabriela Chiosis
Affiliation:
Keywords: Hsp90 chaperone, apoptosis signaling, stress-activated Jun N-terminal kinase, Proteasome Pathway, Tumor Immunogenicity
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.
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Cite this article as:
Brodsky L. Jeffrey and Chiosis Gabriela, Hsp70 Molecular Chaperones: Emerging Roles in Human Disease and Identification of Small Molecule Modulators, Current Topics in Medicinal Chemistry 2006; 6 (11) . https://dx.doi.org/10.2174/156802606777811997
DOI https://dx.doi.org/10.2174/156802606777811997 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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