Heat-induced expression of the immediate-early gene IER5 and its involvement in the proliferation of heat-shocked cells

The serum-inducible and growth factor-inducible gene IER5 encodes a protein that acts as a regulator of cell proliferation. Expression of IER5 is also induced by treatment of cells with ionizing radiation and anticancer agents. In this study, we demonstrate the expression and function of IER5 in heat-shocked cells. Heat treatment causes robust expression of IER5 in a heat shock factor (HSF) 1-dependent manner. HSF1 is the master transcriptional regulator of chaperone genes, and the IER5 promoter contains the binding sequence for HSF1 and is bound by heat-activated HSF1. Proteotoxic stressors, such as celastrol and MG132, are known to activate HSF1, and are potent inducers of HSF1 binding and IER5 expression. Overexpression of IER5 leads to upregulation of chaperone gene expression and to an increase in refolding of heat-denatured proteins. Cells expressing IER5 efficiently recover viability after heat challenge. These observations suggest that HSF1-mediated IER5 expression is involved in the expression of chaperone genes and in recovery from thermal stress.