Heat shock factor protein 1 (HSF1) (HSF1)

Heat shock factor protein 1 (HSF1) is the master transcriptional regulator of the heat shock response, a highly conserved mechanism essential for maintaining cellular proteostasis [1, 2]. Under conditions of proteotoxic stress, such as elevated temperature or oxidative damage, HSF1 undergoes trimerization and nuclear translocation to induce the expression of molecular chaperones like HSP70 and HSP90 [4, 6]. In the context of oncology, HSF1 is frequently overexpressed or hyperactivated, driving a specialized transcriptional program that supports tumor cell survival, metabolic rewiring, and metastasis [1, 12, 15]. Conversely, in neurodegenerative diseases like Alzheimer's and Parkinson's, HSF1 activity is often impaired, leading to the toxic accumulation of misfolded protein aggregates [4, 10]. Therapeutic strategies currently focus on inhibiting HSF1 in cancer to sensitize tumors to stress, while exploring HSF1 activation as a means to enhance protein folding capacity in neurodegeneration [8, 12, 13].

Other names

Heat shock transcription factor 1HSTF1HSF 1Master regulator of the heat shock response

Direct inhibition of DNA binding, inhibition of transcriptional activity by blocking coactivator recruitment, promotion of HSF1 degradation, and indirect activation via HSP90 inhibition [8, 12, 13].