This would require the cell to maintain a stockpile of chaperones for protein folding emergencies.A counter view is that the cell has little excess chaperone capacity, and that the concentration of chaperones is titrated closely to the folding requirements for each client protein within a specific cell type.This would imply that the folding environment in the cell is delicate, which would seem to be a risky proposition.For this to be compatible with the complex and varying reasch YK11 cellular environment, the delicate nature of protein homeostasis would need to be paired with a highly robust stress response that is very sensitive and responds rapidly to any flux in protein biogenesis.Moreover, because chaperones are growthregulated and stressresponsive, they afford the cell with a stress sensor to link stress signaling processes with protein homeostasis. The unfolded protein transitions to the intermediate and native state assisted by molecular chaperones.Likewise, intermediates can form aggregates, become degraded, or fold to the native state assisted by chaperones.GENES DEVELOPMENT that have limited substrate selectivity in eukaryotes, cochaperones provide specificity for interaction with chaperones and specific client proteins. The assembly of macromolecular chaperone complexes containing these specific client proteins is a common structural motif in signal transduction to ensure that proteins whose activities must be precisely regulated are in a hairtrigger conformational state.The folding and assembly of the large and diverse class of steroid aporeceptors emphasizes the importance of intermediate species and conformational choice as a potent step in protein biogenesis.Stress and other physiological demands on protein homeostasis can result in the sporadic and unpredicted flux of conformationally challenged proteins that can alter the chaperonesubstrate balance.Yet, at the same time, the pool of chaperones is essential to protect nascent chains and other metastable proteins from misfolding under normal conditions and when cells are exposed to acute or chronic stress. Stressinduced changes in the absolute and relative levels of chaperones and cochaperones could lead to novel chaperone networks that, in turn, would redirect information flow through alternate folding pathways, with effects on translocation and subcellular localization.Consequently, some signaling pathways may be enhanced or dampened because of changes in the levels of a particular cochaperone or chaperone that affects the stability of the heteromeric complex.Longterm chaperone imbalance, therefore, is likely to have dramatic consequence on diverse cellular processes.Cells that have lost their ability to properly regulate proper growth control, such as tumor cells, often express higher levels of chaperones. This suggests that enhanced levels of chaperones could suppress missense mutations that accumulate during transformation to promote cell growth and oncogenesis.The involvement of chaperones in a multitude of signaling and regulatory pathways offers a challenge to systems biology in which networks are used to organize specific pathways.The expression of chaperones is essential for normal growth and development and to survive stress.The heatshock response enables the cell to elevate the expression of genes that function to protect against proteotoxic stress and to initiate a regulatory cascade for recovery and adaptation. This occurs by a nearly instantaneous induction of heatshock genes proportional to the intensity, duration, and type of stress.

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