Rac1 regulates stress-induced, redox-dependent heat shock factor activation

The signaling pathway by which environmental stresses activate heat shock f actors (HSFs) is not completely understood. We show that the small GTPase r ad, and Rad-regulated reactive oxygen species (ROS) play an important role in stress-stimulated heat shock response. A dominant-negative allele of Rad (Rac1N17) inhibits the hypoxia/reoxygenation and sodium arsenite-induced t ranscriptional activity of HSF-1 and the transcription of heat shock protei n 70. Rac1N17 also suppresses the production of intracellular ROS induced b y hypoxia/reoxygenation or sodium arsenite. Moreover, direct suppression of intracellular ROS levels by antioxidants decreases stress-stimulated HSF a ctivity. However, expression of a constitutively active mutant of Rad (Rac1 V12) in the absence of extracellular stresses does not increase intracellul ar ROS levels or induce the heat shock response. These results show that Ra d is a necessary but insufficient component of the stress-induced signaling pathway that leads to ROS production, activation of HSFs, and transcriptio n of heat shock proteins.