HSF1 and HSF3 cooperatively regulate the heat shock response in lizards

Area of Science:

• Molecular Biology
• Cellular Stress Response
• Evolutionary Biology

Background:

• Cells protect themselves from heat-induced protein misfolding by producing heat shock proteins (HSPs) via the heat shock response (HSR).
• Heat shock transcription factor (HSF) is the primary regulator of the HSR.
• While HSF1 is a key regulator in mammals and HSF3 in birds, the roles of different HSFs in other vertebrates are less understood.

Purpose of the Study:

• To investigate the potential of HSF1 and HSF3 from non-mammalian vertebrates to induce the HSR.
• To explore the cooperative roles of HSF1 and HSF3 in regulating the HSR in lizards and frogs.

Main Methods:

• Isolation of lizard and frog HSF gene cDNA clones.
• Analysis of DNA-binding activity of HSF1 and HSF3 under heat shock conditions.
• Overexpression of HSF1 and HSF3 in mouse cells to assess HSP70 induction.
• Knockdown of HSF1 and HSF3 in lizard cells to evaluate HSR and heat resistance.

Main Results:

• Phylogenetic analysis revealed distinct evolutionary paths for HSF3 across species.
• Both lizard and frog HSF1 and HSF3 proteins exhibited heat-inducible DNA-binding activity.
• Overexpression of HSF1 and HSF3 from lizards and frogs induced HSP70 expression in mouse cells during heat shock.
• Knockdown of either HSF1 or HSF3 in lizard cells impaired HSP70 induction and reduced heat resistance.

Conclusions:

• Both HSF1 and HSF3 possess the capacity to induce the HSR in vertebrate cells.
• HSF1 and HSF3 appear to function cooperatively in regulating the HSR in lizards.
• The HSR in lizards and frogs involves complex regulatory mechanisms involving multiple HSF family members.