Heat shock

Induction of the 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 σ 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. Newly trimerized HSF1 will bind to heat shock elements (HSE) located in promoter regions of different HSPs to activate transcription of HSP mRNA. The mRNA will eventually be transcribed and comprise the upregulated HSPs that can alleviate the stress at hand and restore proteostasis. HSF1 will also regulate expression of HSPs through epigenetic modifications. The HSR will eventually attenuate as HSF1 returns to its monomeric form, negatively regulated through association with HSP70 and HSP90 along with additional post-translational modifications. 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.