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.
Export Options
About this article
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 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Comprehensive Analysis Reveals GPRIN1 is a Potential Biomarker for Non-sm all Cell Lung Cancer
Current Bioinformatics Epidemiology and Pathology of Malignant Mesothelioma
Current Respiratory Medicine Reviews Anti-tumor Drug Targets Analysis: Current Insight and Future Prospect
Current Drug Targets Anti-Tumor Effects of Osthole on Different Malignant Tissues: A Review of Molecular Mechanisms
Anti-Cancer Agents in Medicinal Chemistry Risk Factors for Lung Cancer in Never Smokers: A Recent Review Including Genetics
Current Respiratory Medicine Reviews Regulation of Tumor Angiogenesis by the Immune System
Current Angiogenesis (Discontinued) The Role of Epigenetics in Drug Resistance in Cancer
Epigenetic Diagnosis & Therapy (Discontinued) A Wnt-ow of Opportunity: Targeting the Wnt/β-Catenin Pathway in Breast Cancer
Current Drug Targets The Acute Phase Protein α1-Acid Glycoprotein: A Model for Altered Glycosylation During Diseases
Current Protein & Peptide Science Lactate Transporters and pH Regulation: Potential Therapeutic Targets in Glioblastomas
Current Cancer Drug Targets MDA-7/IL-24-Based Cancer Gene Therapy: Translation from the Laboratory to the Clinic
Current Gene Therapy Histone Deacetylase Inhibitors: Molecular and Biological Activity as a Premise to Clinical Application
Current Drug Metabolism The Means to an End of Tumor Cell Resistance to Chemotherapeutic Drugs Targeting Thymidylate Synthase: Shoot the Messenger
Current Drug Targets P68 RNA Helicase (DDX5) Required for the Formation of Various Specific and Mature miRNA Active RISC Complexes
MicroRNA Investigating the In Vivo Expression Patterns of miR-7 microRNA Family Members in the Adult Mouse Brain
MicroRNA Insulin-Like Growth Factor 2 - The Oncogene and its Accomplices
Current Pharmaceutical Design A New “Era” for the α7-nAChR
Current Drug Targets Development of Pin1 Inhibitors and their Potential as Therapeutic Agents
Current Medicinal Chemistry Malignant Mesothelioma: Biology, Diagnosis and Therapeutic Approaches
Current Molecular Pharmacology Urokinase-a Very Popular Cardiovascular Agent
Recent Patents on Cardiovascular Drug Discovery