Early Events in the Heat Shock Response: Action in the Nucleus

This lecture delves into the early events of the Heat Shock Response (HSR) in eukaryotes, focusing on the Hsf1-dependent induction of proteostasis machinery and the regulation models proposed by David Pincus. Through the study of budding yeast, fundamental mechanisms that regulate Hsf1 are uncovered, including the role of Hsp70 in repressing Hsf1 activity. The lecture explores how non-equilibrium binding endows Hsp70 with 'ultra-affinity' and the impact of J-domain proteins on this process. Additionally, the lecture discusses the 'Hsp70 titration' model, challenges faced by this model, and the dynamic interaction between Hsp70 and Hsf1 during heat shock. The importance of Sis1 in regulating Hsf1 activity and the implications of its conditional depletion from the nucleus are also highlighted.