Heat shock transcription factor HSF2 modulates the autophagy response through the BTG2-SOD2 axis

The heat shock transcription factor HSF1 regulates the inducible Hsp gene transcription, whereas HSF2 is involved in the constitutive transcription. HSFs can work for the non-heat shock genes transcription in a case-specific manner to facilitate normal cellular functions. Here, we demonstrate that HSF2 acts as an upstream regulator of heat shock-induced autophagy response in a rat histiocytoma. The heat-induced HSF2 transactivates the B-cell translocation gene-2 (BTG2) transcription, and the latter acts as a tran-scriptional coactivator for superoxide dismutase (SOD2). The altered HSF2 promoter occupancy on the BTG2 promoter enhances BTG2 transcription. Since SOD2 regulation is linked to mitochondrial redox sensing, HSF2 appears to act as a redox sensor in deciding the cell fate. The HSF2 shRNA or NFE2L2/BTG2 siRNA treatments have interfered with the autophagy response. We demonstrate that HSF2 is an up-stream activator of autophagy response, and the HSF2-BTG2-SOD2 axis acts as a switch between the non-selective (micro/macro) and selective (chaperone-mediated) autophagy. (c) 2022 Elsevier Inc. All rights reserved.

Automated summary

The heat shock transcription factors HSF1 and HSF2 play different roles in regulating transcription in cells. HSF2 acts as an upstream regulator in heat-induced autophagy response by activating the transcription of BTG2 and SOD2. This finding reveals the important role of HSF2 in cellular redox sensing.