A trans-activation domain in yeast heat shock transcription factor is essential for cell cycle progression during stress

Gene expression in response to heat shock is mediated by the heat shock tra nscription factor (HSF), which in yeast harbors both amino- and carboxyl-te rminal transcriptional activation domains. Yeast cells bearing a truncated form of HSF in which the carboxyl-terminal transcriptional activation domai n has been deleted [HSF(1-583)] are temperature sensitive for growth at 37 degrees C, demonstrating a requirement for this domain for sustained viabil ity during thermal stress. Here we demonstrate that HSF(1-583) cells underg o reversible cell cycle arrest at 37 degrees C in the G(2)/M phase of the c ell cycle and exhibit marked reduction in levels of the molecular chaperone Hsp90. As in higher eukaryotes, yeast possesses two nearly identical isofo rms of Hsp90: one constitutively expressed and one highly heat inducible. W hen expressed at physiological levels in HSF(1-583) cells, the inducible Hs p90 isoform encoded by HSP82 more efficiently suppressed the temperature se nsitivity of this strain than the constitutively expressed gene HSC82, sugg esting that different functional roles may exist for these chaperones. Cons istent with a defect in Hsp90 production, HSF(1-583) cells also exhibited h ypersensitivity to the Hsp90-binding ansamycin antibiotic geldanamycin. Dep letion of Hsp90 from yeast cells wild type for HSF results in cell cycle ar rest in both G(1)/S and G(2)/M phases, suggesting a complex requirement for chaperone function in mitotic division during stress.