Upregulation of the Hsp104 chaperone at physiological temperature during recovery from thermal insult

Thermal insult at 50degreesC causes protein denaturation in yeast, but the cells survive if preconditioned at 37degreesC. Survival depends on refolding of heat-denatured proteins. Refolding of cytoplasmic proteins requires Hsp104, the expression of which increases several-fold upon shift of the cells from physiological temperature 24degreesC to 37degreesC. We describe here a novel type of regulation of Hsp104, designated delayed upregulation (DUR). When Saccharomyces cerevisiae cells grown at 24degreesC, preconditioned at 37degreesC and treated briefly at 50degreesC were shifted back to 24degreesC, Hsp104 expression was negligible for 1 h, but increased then to a three to nine times higher level than that detected after growth at 24degreesC, returning to normal after 5 h. A heat shock element (HSE) of the upstream sequence of HSP104 was necessary and sufficient for DUR, whereas stress response elements (STRE) were dispensable. Destruction of HSE plus all three STREs abolished Hsp104 expression, resulting in cell death after thermal insult. Deletion of MSN2/4, encoding transcription factors driving STRE-dependent gene expression, decreased DUR. Deletion of HOG1, encoding a heat-responsive and osmosensitive mitogen-activated protein kinase implicated to be functionally connected to Msn2/4p, abolished DUR. We suggest that DUR was regulated via HSE, required Hog1p and involved Msn2/4p-regulated gene products.