The heat shock response (HSR) pathway. The mammalian HSR is governed by the transcription factor HSF-1. In absence of stress, chaperones maintain HSF-1 as an inert monomer. With the appearance of misfolded proteins in the cytoplasm, chaperones are titrated away from HSF-1 (1) to deal with misfolding and aggregation. This allows HSF-1 to trimerize (2), bind to its consensus sequence (3) and be post-translational modified (4) therefore inducing the transcription of chaperones and heat shock proteins (hsps) (5). HSF-1 activation pathway is negatively regulated by the newly expressed chaperones and hsps, which rebind HSF-1 (6), and by acetyl transferases (HATs) (7). SIRT1 positively regulates HSF1 DNA-binding activity (7).