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

The roles of heat shock transcription factors (HSFs) under physiological conditions have recently become the focus of intense study. We generated avian cells lacking two heat-inducible HSFs, HSF1 and HSF3. In addition to complete loss of activation of heat shock genes under stress conditions, these cells exhibited a marked reduction in Hsp90α expression under normal growth conditions. Reduction in Hsp90α expression caused instability of a cyclin-dependent kinase, Cdc2, and cell cycle progression was blocked mainly at the G(2) phase, but also at G(1) phase even at mild heat shock temperatures. Restoration of Hsp90α expression rescued the temperature sensitivity without induction of Hsps. We demonstrated for the first time a molecular target affected by heat shock in vivo that causes cell cycle arrest in vertebrates and a novel mechanism of stress resistance controlled by vertebrate HSFs.