Members of the HSP70 family form a central hub of the molecular chaperone network, controlling protein homeostasis in prokaryotes and in the ATP-containing compartments of the eukaryotic cells. The heat-inducible form HSPA1A (HSP70), its constitutive cytosolic cognate HSPA8 (Hsc70), its endoplasmic reticulum form HSPA5 (BiP), and its mitochondrial form HSPA9 (Mortalin), as well as the more distantly related HSPHs (HSP110s), make up 1-2 % of the total mass of proteins in human cells. They use the energy of ATP-hydrolysis to prevent and forcefully revert the process of protein misfolding and aggregation during and following various stresses, presumably by working as unfoldases to lift aberrant conformers out of kinetic traps. As such, HSP70s, in cooperation with their J-domain co-chaperones and nucleotide exchange factors (NEFs) and co-disaggregases, form an efficient network of cellular defenses against the accumulation of cytotoxic misfolded protein conformers, which may cause degenerative diseases such as Parkinson's and Alzheimer's disease, diabetes, and aging in general. In addition to their function in repair of stress-induced damage, HSP70s fulfill many housekeeping functions, including assisting the de novo folding and maturation of proteins, driving the translocation of protein precursors across narrow membrane pores into organelles, and by controlling the oligomeric state of key regulator protein complexes involved in signal transduction and vesicular trafficking. For reasons not well understood, HSP70s are also found on the surface of some animal cells, in particular cancer cells where they may serve as specific targets for cancer immunotherapy. Here, we gathered seven mini reviews, each presenting a complementary aspect of HSP70’s structure and function in bacteria and eukaryotes, under physiological and stressful conditions. These articles highlight how, the various members of this conserved family of molecular chaperones, assisted by their various J-domain and NEF cochaperones and co-disaggregases, harness ATP hydrolysis to perform a great diversity of life-sustaining cellular functions using a similar molecular mechanism.

This unique volume reviews the beautiful architectures and varying mechanical actions of the set of specialized cellular proteins called molecular chaperones, which provide essential kinetic assistance to processes of protein folding and unfolding in the cell. Ranging from multisubunit ring-shaped chaperonin and Hsp100 machines that use their central cavities to bind and compartmentalize action on proteins, to machines that use other topologies of recognition — binding cellular proteins in an archway or at the surface of a 'clamp' or at the surface of a globular assembly — the structures show us the ways and means the cell has devised to assist its major effectors, proteins, to reach and maintain their unique active forms, as well as, when required, to disrupt protein structure in order to remodel or degrade. Each type of chaperone is beautifully illustrated by X-ray and EM structure determinations at near- atomic level resolution and described by a leader in the study of the respective family. The beauty of what Mother Nature has devised to accomplish essential assisting actions for proteins in vivo is fully appreciable.

The precise shape of a protein is a crucial factor in its function. How do proteins become folded into the right conformation? Molecular chaperones and protein folding catalysts bind to developing polypeptides in the cytoplasm and ensure correct folding and transport. This Guidebook catalogues the latest information on nearly 200 of these molecules, including the important class of heat shock proteins; each entry is written by leading researchers in the field.

One of the most intriguing discoveries in molecular biology in the last decade is the existence of an evolutionary conserved and essential system, consisting of molecular chaperones and folding catalysts, which promotes the folding of the proteins in the cell. This text summarizes our current knowledge of the cellular roles, the regulation and the mechanism of action of this system. It has a broad scope, covering cell biological, genetic and biochemical aspects of protein folding in cells from bacteria to man. Particularly appropriate to researchers working in basic and applied aspects of molecular medicine, this volume should also prove useful as an up-to-date reference book and as a textbook for specialized university courses.

This volume of Advances in Protein Chemistry provides a broad, yet deep look at the cellular components that assist protein folding in the cell. This area of research is relatively new--10 years ago these components were barely recognized, so this book is a particularly timely compilation of current information. Topics covered include a review of the structure and mechanism of the major chaperone components, prion formation in yeast, and the use of microarrays in studying stress response. Outlines preceding each chapter allow the reader to quickly access the subjects of greatest interest. The information presented in this book should appeal to biochemists, cell biologists, and structural biologists.

This book makes a novel synthesis of the molecular aspects of the stress response and long term adaptation processes with the system biology approach of biological networks. Authored by an exciting mixture of top experts and young rising stars, it provides a comprehensive summary of the field and identifies future trends.

Heat shock proteins are emerging as important molecules in the development of cancer and as key targets in cancer therapy. These proteins enhance the growth of cancer cells and protect tumors from treatments such as drugs or surgery. However, new drugs have recently been developed particularly those targeting heat shock protein 90. As heat shock protein 90 functions to stabilize many of the oncogenes and growth promoting proteins in cancer cells, such drugs have broad specificity in many types of cancer cell and offer the possibility of evading the development of resistance through point mutation or use of compensatory pathways. Heat shock proteins have a further property that makes them tempting targets in cancer immunotherapy. These proteins have the ability to induce an inflammatory response when released in tumors and to carry tumor antigens to antigen presenting cells. They have thus become important components of anticancer vaccines. Overall, heat shock proteins are important new targets in molecular cancer therapy and can be approached in a number of contrasting approaches to therapy.