The most important interactions between cellular molecules have a high affinity, areunique and specific, and require a network approach for a detailed description.Molecular chaperones usually have many first and second neighbors in protein-proteininteraction networks and they play a...

The transition from normal growth conditions to stressful conditions is accompanied bya robust upregulation of heat shock proteins, which dampen the cytotoxicity caused bymisfolded and denatured proteins. The most prominent part of this transition occurson the transcriptional level. In...

Labile or mutation-sensitised proteins may spontaneously convert into aggregation-proneconformations that may be toxic and infectious. This hazardous behavior, whichcan be described as a form of “molecular criminality”, can be actively counteracted in thecell by a network of molecular...

Network theory is increasingly accepted as a basic regulatory mechanism in diverseimmunological functions. Heat shock proteins (Hsps) are involved in multiplenetworks in the immune system. Hsps themselves (foreign or endogenous) activateinnate immunity and play important roles to deliver...

Hsp90 is an essential and ubiquitous molecular chaperone that is required for the properfolding of a set of client proteins at a late stage in their folding process. In eukaryotes,cytoplasmic Hsp90 is absolutely essential for cell viability under all growth conditions.The functional cycle...

The generic tendency of proteins to misassemble into nonfunctional, and sometimescytotoxic, structures poses a universal problem for all types of cell. This problem isexacerbated by the high total concentration of macromolecules found within most intracellularcompartments but it is solved...

Trehalose is a disaccharide of glucose that is found at high concentrations in a widevariety of organisms that naturally survive drying in nature. Many years ago wereported that this molecule has the remarkable ability to stabilize membranes and proteinsin the dry state. A mechanism for the...

Cells possess effective mechanisms to cope with chronic or acute disturbance of homeostasis. Key roles in maintaining or restoring homeostasis are played by the various heat shock or stress proteins (Hsps). Among the Hsps, the group of proteins characterized by low molecular masses (between 20 to...

The most abundant cytoplasmic chaperone of eukaryotic cells, Hsp90 is a hubin developmental regulatory networks and the first example described of thephenomenon of molecular buffering. As a chaperone for many different signalingproteins, Hsp90 maintains the clarity and strength of...

The efficiency, divergence and specificity of virtually all intracellular metabolic andsignalling pathways largely depend on their compartmentalized organization. Acorollary of the requirement of compartmentalization is the dynamic structural partitionof the intracellular space by...

The endoplasmic reticulum is the site of entry into the secretory pathway and representsa major and particularly crowded site of protein biosynthesis. In addition to thecomplexity of protein folding in any organelle, the ER environment poses furtherdangers and constraints to the process. A...

Heat shock (HS), like many other stresses, induces specific and highly regulatedsignaling cascades that promote cellular homeostasis. The three majormitogen-activated protein kinases (MAPK) and protein kinase B (PKB/Akt) are themost notable of these HS-stimulated pathways. Their activation...

The heat shock protein response appears to be triggered primarily by nonnative proteinsaccumulating in a stressed cell and results in increased expression of heat shock proteins(HSPs). Many heat shock proteins prevent protein aggregation and participate in refoldingor elimination of...

A number of observations have lent support to a model in which thermal stress is trans- duced into a signal at the level of the cellular membranes. Our alternative, but not exclusive, approach is based on the concept that the initial stress-sensing events are associated with the physical...

The physiological adjustment of organisms in response to temperature variation is acrucial part of coping with environmental stress. An important component of the coldresponse is the increase in membrane lipid unsaturation, and this has been linked to anenhanced resistance to the...

A growing number of human neurodegenerative diseases are associated with the expressionof misfolded proteins that oligomerize and form aggregate structures. Over time,accumulation of misfolded proteins leads to the disruption of cellular protein foldinghomeostasis and eventually to cellular...