Adaptation to heat stress by diversification of the vertebrate heat shock transcription factor family

Abstract Cells survive and reproduce by coping with acute or chronic exposure to a fixed elevated temperature or fluctuating temperatures. These properties are one of the main evolutionary forces and involve the heat shock response. This response is characterized by the induction of heat-shock proteins (HSPs) and is mainly regulated by heat-shock transcription factors (HSFs) in vertebrates. A single HSF is present in yeast and invertebrates, such as Caenorhabditis elegans and Drosophila, whereas vertebrates have evolved multiple HSFs. The potential of HSFs to induce HSP expression is linked to the amino acid conservation of their domains and regions that are responsible for transcriptional activation and appears to be associated with the homeothermic capacity of vertebrate animals in a thermally fluctuating environment. HSFs protect cells and organisms from heat stress by regulating not only their expression of HSPs that assist in protein folding and suppress protein misfolding and aggregation, but also the expression of genes related to protein clearance, metabolism, the cell cycle, DNA damage response, apoptosis, senescence, the cytoskeleton, extracellular matrix and inflammation. The diversification of HSF genes may expand the cellular capacity to adapt to thermal changes in vertebrate animals. This article is part of the Theo Murphy meeting issue ‘ProteostaSys: a systems view of proteostasis’.