HSF1 GRANULES - A NOVEL STRESS-INDUCED NUCLEAR COMPARTMENT OF HUMAN-CELLS

Heat shock factor 1 (HSF1) is the ubiquitous stress-responsive transcr iptional activator which is essential for the inducible transcription of genes encoding heat shock proteins and molecular chaperones. HSF1 l ocalizes within the nucleus of cells exposed to heat shock, heavy meta ls, and amino acid analogues, to form large, irregularly shaped, brigh tly staining granules which are not detected during attenuation of the heat shock response or when cells are returned to their normal growth conditions. The kinetics of detection of HSF1 granules parallels the transient induction of heat shock gene transcription. HSF1 granules ar e also detected using an HSF1-Flag epitope tagged protein or a chimeri c HSF1-green fluorescent protein which reveals that these nuclear stru ctures are stress-induced and can be detected in living cells, The spa tial organization of HSF1 granules in nuclei of stressed cells reveals that they are novel nuclear structures which are stress-dependent and provides evidence that the nucleus undergoes dynamic reorganization i n response to stress.