Cell cycle transition under stress conditions controlled by vertebrate heat shock factors

The roles of heat shock transcription factors (HSFs) under physiological co nditions have recently become the focus of intense study. We generated avia n cells lacking two heat-inducible HSFs, HSF1 and HSF3. In addition to comp lete loss of activation of heat shock genes under stress conditions, these cells exhibited a marked reduction in Hsp90 alpha expression under normal g rowth conditions. Reduction in Hsp90 alpha expression caused instability of a cyclin-dependent kinase, Cdc2, and cell cycle progression was blocked ma inly at the G(2) phase, but also at G(1) phase even at mild heat shock temp eratures, Restoration of Hsp90 alpha, expression rescued the temperature se nsitivity without induction of Hsps. We demonstrated for the first time a m olecular target affected by heat shock in vivo that causes cell cycle arres t in vertebrates and a novel mechanism of stress resistance controlled by v ertebrate HSFs.