Heat shock response

With the introduction of environmental stressors, the cell must be able to maintain proteostasis. Acute or chronic subjection to these harmful conditions elicits a cytoprotective response to promote stability to the proteome. HSPs (e.g. HSP70, HSP90, HSP60, etc.) are present under normal conditions but under heat stress, they are upregulated by the transcription factor heat shock factor 1 (HSF1). There are four different transcription factors found in vertebrates (HSF 1–4) where the main regulator of HSPs is HSF1, while σ32 is the heat shock transcription factor in E. coli. When not bound to DNA, HSF1 is in a monomeric state where it is inactive and negatively regulated by chaperones. When a stress occurs, these chaperones are released due to the presence of denatured proteins and various conformational changes to HSF1 cause it to undergo nuclear localization where it becomes active through trimerization. The HSR is not only involved with increasing transcription levels of HSPs; other facets include stress-induced mRNA stability preventing errors in mRNA and enhanced control during translation to thwart misfolding. ==Molecular chaperones==

Molecular chaperones are typically referred to as proteins that associate with and help other proteins reach a native conformation while not being present in the end state. Chaperones bind to their substrate (i.e. a misfolded protein) in an ATP-dependent manner to perform a specific function. Exposed hydrophobic residues are a major problem with regards to protein aggregation because they can interact with one another and form hydrophobic interactions. It is the job of chaperones to prevent this aggregation by binding to the residues or providing proteins a "safe" environment to fold properly. Heat shock proteins are also believed to play a role in the presentation of pieces of proteins (or peptides) on the cell surface to help the immune system recognize diseased cells. The major HSPs involved in the HSR include HSP70, HSP90, and HSP60. When a nascent protein is being translated, HSP70 is able to associate with the hydrophobic regions of the protein to prevent faulty interactions until translation is complete. Post-translational protein folding occurs in a cycle where the protein becomes bound/released from the chaperone allowing burying hydrophobic groups and aiding in overcoming the energy needed to fold in a timely fashion. HSP70 plays a part in de-aggregating proteins using the aforementioned mechanism; the chaperone will bind to exposed hydrophobic residues and either partially or fully disassemble the protein, allowing HSP70 to assist in the proper refolding. When proteins are beyond the point of refolding, HSP70s can help direct these potentially toxic aggregates to be degraded by the proteasome or through autophagy. HSP90s are parallel to HSP70s with respect to the refolding or proteins and use in protein clearance. Once a cap binds to the chaperonin, the protein is free within the barrel to undergo hydrophobic collapse and reach a stable conformation. Once the cap is removed, the protein can either be correctly folded and move on to perform its function or return to a HSP if it is still not folded accurately. These chaperones function to remove aggregation and significantly speed up protein folding. ==Discovery==

Discovery of the heat shock response is attributed to Italian geneticist Ferruccio Ritossa, who observed changes called chromosomal "puffs" in response to heat exposure while working with the polytene chromosomes of Drosophila. By his own account, the discovery was the serendipitous result of unintentional elevated temperature in a laboratory incubator. Ritossa's observations, reported in 1962, were later described as "the first known environmental stress acting directly on gene activity" The significance of these observations became clearer in the 1970s, as a distinct class of heat shock proteins were discovered in the laboratory of Herschel K. Mitchell, and as heat shock responses were reported in other organisms and came to be recognized as universal. == See also ==