Environmental regulation of yeast prions.

Abstract

<p>Prionogenesis is a multistep process in which the prion determinant protein undergoes changes in its secondary structure to form intermediate species and then prion (amyloid) fibrils; this process relies on other cellular machinery to drive these changes. Thermal stress results in the relocalization of heat-shock factor 1 (Hsf1) from the cytoplasm to the nucleus; here it binds to the heat-shockelement (HSEs) of heat-shock–protein genes, activating their transcription. Consequentially, a diverse group of heat-shock proteins (HSPs) are synthesized. Many HSPs (molecular chaperones) play important roles in prion formation and propagation, including Hsp104, Hsp70-Ssa, and Hsp40-Sis1. In a similar manner, general stresses including oxidative, osmotic, and heat stresses, activate a separate pathway in which Msn2,4 binds to the stress-response element (STREs) of stress-response genes, thereby activating their transcription. Some HSP genes also contain one or more STREs at their 5′-regulatory regions. Deletion of the <i>MSN2</i> gene results in a drastic increase of the frequency of [<i>PSI</i>⁺] formation, suggesting that some stress-response proteins are also involved in prion formation. However, the identity of the Msn2,4 targets that are involved in prionogenesis remain elusive. Note: for simplicity, only the two major stress-response pathways that are regulated by Hsf1 and Msn2,4 are shown.</p