Redefining proteostasis transcription factors in organismal stress responses, development, metabolism and health

Eukaryotic organisms have evolved complex and robust cellular stress response pathways to ensure maintenance of proteostasis and survival during fluctuating environmental conditions. Highly conserved stress response pathways can be triggered and coordinated at the cell autonomous and cell-non-autonomous level by proteostasis transcription factors, including HSF1, SKN-1/Nrf2, HIF1 and DAF-16/FOXO that combat proteotoxic stress caused by environmental challenges. While these transcription factors are often associated with a specific stress condition, they also direct “non-canonical” transcriptional programmes that serve to integrate a multitude of physiological responses required for development, metabolism and defence responses to pathogen infections. In this review we outline the established function of these key proteostasis transcription factors at the cell-autonomous and cell-non-autonomous level and discuss a newly emerging stress responsive transcription factor, PQM-1, within the proteostasis network. We look beyond the canonical stress response roles of proteostasis transcription factors and highlight their function in integrating different physiological stimuli to maintain cytosolic organismal proteostasis.