The mTOR Target S6 Kinase Arrests Development in When the Heat-Shock Transcription Factor Is Impaired.

The widely conserved heat-shock response, regulated by heat-shock transcription factors, is not only essential for cellular stress resistance and adult longevity, but also for proper development. However, the genetic mechanisms by which heat-shock transcription factors regulate development are not well understood. In , we conducted an unbiased genetic screen to identify mutations that could ameliorate the developmental-arrest phenotype of a heat-shock factor mutant. Here, we show that loss of the conserved translational activator S6 kinase, a downstream effector of mechanistic Target of Rapamycin (mTOR) kinase, can rescue the developmental-arrest phenotype of partial loss-of-function mutants. Unexpectedly, we show that the rescue is not likely caused by reduced translation, nor by activation of any of a variety of stress-protective genes and pathways. Our findings identify an as-yet unexplained regulatory relationship between the heat-shock transcription factor and the mTOR pathway during development.