Jy. Zou et al., REPRESSION OF HEAT-SHOCK TRANSCRIPTION FACTOR HSF1 ACTIVATION BY HSP90 (HSP90 COMPLEX) THAT FORMS A STRESS-SENSITIVE COMPLEX WITH HSF1, Cell (Cambridge), 94(4), 1998, pp. 471-480
Heat shock and other proteotoxic stresses cause accumulation of nonnat
ive proteins that trigger activation of heat shock protein (Hsp) genes
. A chaperone/Hsp functioning as repressor of heat shock transcription
factor (HSF) could make activation of hsp genes dependent on protein
unfolding. In a novel in vitro system, in which human HSF1 can be acti
vated by nonnative protein, heat, and geldanamycin, addition of Hsp90
inhibits activation. Reduction of the level of Hsp90 but not of Hsp/c7
0, Hop, Hip, p23, CyP40, or Hsp40 dramatically activates HSF1. In vivo
, geldanamycin activates HSF1 under conditions in which it is an Hsp90
-specific reagent. Hsp90-containing HSF1 complex is present in the uns
tressed cell and dissociates during stress. We conclude that Hsp90, by
itself and/or associated with multichaperone complexes, is a major re
pressor of HSF1.