Fig. 1

Heat shock response and HSP70 function. The Activation of the heat shock response after non-lethal stress. (I) At rest HSF-1 is inactive in a monomeric state bonded with the cytosolic HSP70s, located in the cytosol. P: Functional Proteins. (II) Under stress conditions and in the presence of denatured proteins (DP), HSP70 releases HSF-1 and subsequently binds to denatured proteins, acting as chaperones (aiding protein refolding) and releasing HSF. Serine-phosphorylation and trimerisation of HSF-1 induces enhanced HSF-1 DNA binding affinity. The binding of the trimeric HSF to HSE initiates the transcription of the HSP mRNA. Additionally, SIRT1 prolongs HSF1 binding to the promoters of heat shock genes by maintaining HSF1 in a deacetylated form. (III) After recovery from stress, HSP70 rebinds to HSF-1 so exerting an inhibitory effect on HSF-1/HSE binding. Overall, stress adaptation is associated with increased levels of HSP70