Regulation of Hsf1 by Rim15 Kinase

Abstract

Hsf1, Heat Shock transcription Factor in yeast, is always in a form of a homotrimer within the nucleus and is involved in not only constitutive but also stress-inducible binding to heat shock elements(HSEs) within certain promoters. Activation of Hsf1 is considered to be induced by changes in conformation through either direct sensing of elevated temperature, oxidants or low pH, or by phosphorylation for cellular homeostasis. It has been shown that Yak1, which is under the negative control of PKA, can activate Hsf1 at the level of DNA binding by direct phosphorylation under the conditions of low PKA activity. However, based on the fact that Hsf1 was still activated in yak1△, it was postulated that Yak1 might not be the only downstream kinase of PKA engaged in Hsf1 activation. In this study, Rim15, a protein kinase required for the proper entry into the stationary phase(G0), was identified as an additional kinase which can directly phosphorylate and activate Hsf1 upon glucose starvation. In addition, Rim15 is known to activate Msn2 and Gis1 transcription factors. However, Rim15 was demonstrated to phosphorylate Msn2, but not Gis1, in vitro. . These results suggest diverse mechanisms of Rim15 in regulation of stress-responsive transcription factors.