Trehalose is a positive regulator of the heat-induced activity of yeast heat shock transcription factor

The heat shock transcription factor (Hsf1) is a stress-responsive transcriptional regulator of heat shock genes. Hsf1 is primarily under negatively regulation under constitutive conditions. Following a mild stress, such as heat shock, Hsf1 is able to evoke a high level of HSP expression. This dramatic increase in activity may involve several factors, including post-translational modifications, protein-protein interactions, and conformational changes. The intracellular concentration of trehalose also increases rapidly in response to many environmental stresses, including heat shock. These high trehalose levels have been correlated with tolerance to adverse conditions and led to the model that trehalose functions as a chemical co-chaperone, working to protect proteins at the initial stages of the heat shock response. To understand how Hsf1 is regulated upon heat stress, the relationship between trehalose and Hsf1 transcriptional activity was investigated. Here, I suggest that trehalose plays a role in increasing Hsf1 transcriptional activity during the heat shock response. Yeast strains with low levels of trehalose have a diminished transcriptional response to heat shock, while strains with high levels of trehalose have an enhanced transcriptional response to heat shock. This transcriptional response is independent of the other known heat responsive transcription factors, Msn2/4, and dependent on Hsf1. The mechanism by which trehalose influences Hsf1 activity was examined further by several methods, and while several avenues have been fruitful, the exact mechanism of trehalose action upon Hsf1 has not yet been elucidated. These in vivo results, together with previous structural data from our laboratory, support a new role for trehalose, where trehalose directly modifies the dynamic range of Hsf1 activity and therefore influences heat shock protein (HSP) mRNA levels in response to stress.