Rabbit Anti-Human HSF2 (a.a. 2-108) Polyclonal antibody

We have examined reporter gene (beta-gal) expression directed by human heat shock transcription factors 1 and 2 (HSF1 and HSF2) in HeLa cells and in yeast (Saccharomyces cerevisiae). Transcriptional activation domains of both HSFs were mapped to the C-termini using chimeric proteins containing the GAL4 DNA binding domain (GAL4-DBD). Deletion analysis of HSF1 largely confirmed the mapping and expression pattern of activation domain 2 (AD2) previously reported by Green et al (1995) with the exception of the contribution of the oligomerization domain (hydrophobic region A) to basal repression in yeast, but not in HeLa cells. in addition, a G-terminal activation domain for HSF2 (amino acids 397 to 536) was identified by analysis in yeast. In contrast to HSF1, full length HSF2 and the isolated activation domain of HSF2 showed little activity in HeLa cells. Analysis of point mutations generated by low fidelity PCR within AD2 of HSF1 indicated that hydrophobic and charged amino acids in addition to proline, serine and threonine make critical contributions to transcriptional activity. Co-expression of GAL4-DBD fusions with AD2 of HSF1 and the C-terminal activation domain of HSF2 showed no evidence of synergism in the activation of transcription. Wildtype human HSF1 and HSF2 were both able to substitute for the endogenous yeast HSF under normal growth conditions.

Maintenance of protein homeostasis, through inducible expression of molecular chaperones, is essential for cell survival under protein-damaging conditions. The expression and DNA-binding activity of heat shock factor 2 (HSF2), a member of the heat shock transcription factor family, increase upon exposure to prolonged proteotoxicity. Nevertheless, the specific roles of HSF2 and the global HSF2-dependent gene expression profile during sustained stress have remained unknown. Here, we found that HSF2 is critical for cell survival during prolonged proteotoxicity. Strikingly, our RNA sequencing (RNA-seq) analyses revealed that impaired viability of HSF2-deficient cells is not caused by inadequate induction of molecular chaperones but is due to marked downregulation of cadherin superfamily genes. We demonstrate that HSF2-dependent maintenance of cadherin-mediated cell-cell adhesion is required for protection against stress induced by proteasome inhibition. This study identifies HSF2 as a key regulator of cadherin superfamily genes and defines cell-cell adhesion as a determinant of proteotoxic stress resistance.