Formation of nuclear stress granules involves HSF2 and coincides with the nucleolar localization of Hsp70

Abstract

The heat-shock response is characterized by the activation of heat-shock transcription factor 1 (HSF1), followed by increased expression of heat-shock proteins (Hsps). The stress-induced subnuclear compartmentalization of HSF1 into nuclear stress granules has been suggested to be an important control step in the regulation of stress response and cellular homeostasis in human cells. In this study, we demonstrate that the less-well characterized HSF2 interacts physically with HSF1 and is a novel stress-responsive component of the stress granules. Based on analysis of our deletion mutants, HSF2 influences to the localization of HSF1 in stress granules. Moreover, our results indicate that the stress granules are dynamic structures and suggest that they might be regulated in an Hsp70-dependent manner. The reversible localization of Hsp70 in the nucleoli strictly coincides with the presence of HSF1 in stress granules and is dramatically suppressed in thermotolerant cells. We propose that the regulated subcellular distribution of Hsp70 is an important regulatory mechanism of HSF1-mediated heat shock response.

Heat Shock Factor 2 (HSF2) Contributes to Inducible Expression of hsp Genes through Interplay with HSF1

“…During hemin treatment we observed binding of HSF1 and HSF2 to the hsp70 promoter (Fig. 1B), which is in line with previous studies (23,25,36,(45)(46)(47). To our surprise, HSF2 was found on the hsp70 promoter also upon heat shock (Fig.…”

“…To our surprise, HSF2 was found on the hsp70 promoter also upon heat shock (Fig. 1B), which is in contrast to previous studies (23,25,36,(45)(46)(47). This finding was consistent in repeated experiments and is quantified in Fig.…”

“…Similar to HSF1, HSF2 has been shown to translocate to punctuated structures in the nucleus of heat-shocked HeLa cells (35). Subsequently, we observed that during heat shock, HSF1 and HSF2 co-localize in the nuclear stress bodies, and a direct interaction between HSF1 and HSF2 during both control and heat shock treatment has been demonstrated (36,37). Reporter assays have suggested that HSF2 is able to potentiate HSF1-mediated transactivation (37).…”

“…Another aspect by which HSF1 might regulate HSF2 activity is through localization. In primate cells, HSF1 and HSF2 are found both in nuclear stress bodies (35,36) and on target gene promoters, and the available pool of nuclear HSFs needs to be divided between these structures. Previous studies by Alastalo et al (36) show that expression of a mutant HSF2 lacking the DNA-binding domain prevented the localization of either HSF1 or HSF2 to nuclear stress bodies, suggesting that also in this respect the interplay between these two factors is important.…”

Is a New Immune Response Mediator in the NF-κB pathway - SUMO-4 - Related to Type 1 Diabetes?

“…No such effect was observed with the expression of the SUMO4*M55V variant. HSF1 and HSF2 are known to regulate the expression of heat shock protein (HSP) genes [20,21], and enhanced production of HSPs has been observed in pancreatic β-cells exposed to proinflammatory cytokines [6]. It is therefore possible that SUMO4*M conjugated HSF1 and HSF2 are ineffective in mediating downregulation of HSP generation during insulitis to protect pancreatic islet cells from undergoing apoptosis.…”