Heat shock response

[5] If the work by molecular chaperones is not enough to prevent incorrect folding, the protein may be degraded by the proteasome or autophagy to remove any potentially toxic aggregates.

[14] 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.

[15][14] 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.

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.

[20] It is the job of chaperones to prevent this aggregation by binding to the residues or providing proteins a "safe" environment to fold properly.

[24] Sometimes, HSP70 is unable to effectively aid a protein in reaching its final 3-D structure; The main reason being the thermodynamic barriers for folding are too high for the chaperone to meet.

[28] Once a cap binds to the chaperonin, the protein is free within the barrel to undergo hydrophobic collapse and reach a stable conformation.

[33] Ritossa's observations, reported in 1962,[34] were later described as "the first known environmental stress acting directly on gene activity"[31] but were not initially widely cited.