Abstract
Cells cope with temperature elevations, which cause protein misfolding, by expressing heat shock proteins (HSPs). This adaptive response is called the heat shock response (HSR), and it is regulated mainly by heat shock transcription factor (HSF). Among the four HSF family members in vertebrates, HSF1 is a master regulator of HSP expression during proteotoxic stress including heat shock in mammals, whereas HSF3 is required for the HSR in birds. To examine whether only one of the HSF family members possesses the potential to induce the HSR in vertebrate animals, we isolated cDNA clones encoding lizard and frog HSF genes. The reconstructed phylogenetic tree of vertebrate HSFs demonstrated that HSF3 in one species is unrelated with that in other species. We found that the DNA-binding activity of both HSF1 and HSF3 in lizard and frog cells was induced in response to heat shock. Unexpectedly, overexpression of lizard and frog HSF3 as well as HSF1 induced HSP70 expression in mouse cells during heat shock, indicating that the two factors have the potential to induce the HSR. Furthermore, knockdown of either HSF3 or HSF1 markedly reduced HSP70 induction in lizard cells and resistance to heat shock. These results demonstrated that HSF1 and HSF3 cooperatively regulate the HSR at least in lizards, and suggest complex mechanisms of the HSR in lizards as well as frogs.
Highlights
All living cells must maintain the appropriate conformations and physiological concentrations of proteins, which is known as protein homeostasis or proteostasis, by keeping a balance between the synthesis, folding, and clearance of individual proteins [1,2,3]
We performed RT-PCR using primers that were mainly designed on the basis of RNA sequence data from A. sagrei [30], and we isolated HSF1, HSF2, and HSF3 cDNA clones from the hindlimb, and HSF4 cDNA clones from the eye [13]
The sequences of regions X and Y in HSF1s and HSF2s as well as those of region X in HSF4s are highly conserved among vertebrate species, whereas the sequences in these two regions in HSF3s are less well conserved (Fig 1)
Summary
All living cells must maintain the appropriate conformations and physiological concentrations of proteins, which is known as protein homeostasis or proteostasis, by keeping a balance between the synthesis, folding, and clearance of individual proteins [1,2,3]. To adapt to temperature elevations, which cause protein unfolding and misfolding, cells have evolved sophisticated mechanisms that adjust proteostasis capacity or buffering capacity against protein misfolding [4]. One such evolutionally conserved mechanism is the heat shock response (HSR), which is characterized by the induction of heat shock proteins (HSPs) or chaperones, and facilitates proper folding of cellular proteins [5]. The HSR is mainly regulated at the level of transcription by the widely
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
