Chaperone-Mediated Repression

Abstract

Chaperone proteins are implicated not only in aiding the formation of properly folded and functional signaling proteins, but also in subsequent control of the activity of their protein targets. In particular the Hsp90- and Hsp70-type chaperone proteins take part in assembly of nuclear receptor complexes and control of transcription by those receptors (see STKE Perspective by DeFranco and Csermely ). Hon et al. now present evidence for similar, yet distinct, roles for chaperone proteins of these types in control of the heme activator protein (Hap1) in the yeast Saccharomyces cerevisiae . Yeast respond to oxygen with increased production of heme protein, which activates Hap1 transcription factor to promote transcription of genes whose products function in respiration and protection from oxygen damage. In the absence of heme, the transcriptional activity of Hap1 is normally repressed by interactions with cellular proteins, including Hsp90 and now the Hsp70 proteins designated Ssa and Sro9. Decreased expression of the Hsp70 Ssa (and, to a lesser extent, decreased expression of Sro or its partner Ydj1) caused enhanced transcriptional and DNA binding activity of Hap1 in the absence of heme, but did not affect Hap1 activity in the presence of high concentrations of heme. This contrasts with the effect of Hsp90 on Hap1 or on nuclear receptors. Loss of Hsp90 does not lead to activation, but rather reduces transcriptional activity of its partners even in the presence of activators (steroid hormones or heme). The authors note that distinct modes of regulation of Hap1 activity by the Hsp70 and Hsp90 chaperones provide a means for precise regulation of Hap1 that reveals previously unrecognized versatility in the control of transcription in complexes with multiple chaperones. T. Hon, H. C. Lee, A. Hach, J. L. Johnson, E. A. Craig, H. Erdjument-Bromage, P. Tempst, L. Zhang, The Hsp70-Ydj1 molecular chaperone represses the activity of the heme activator protein Hap1 in the absence of heme. Mol. Cell. Biol . 21 , 7923-7932 (2001). [Abstract] [Full Text] D. B. DeFranco, P. Csermely, Steroid receptor and molecular chaperone encounters in the nucleus. Science's STKE (2000), http://www.stke.org/cgi/content/full/OC_sigtrans;2000/42/pe1 [Summary] [Full Text]