HEAT-SHOCK PROTEIN HSP70 ACCELERATES THE RECOVERY OF HEAT-SHOCKED MAMMALIAN-CELLS THROUGH ITS MODULATION OF HEAT-SHOCK TRANSCRIPTION FACTORHSF1

The role of mammalian 70-kDa heat shock protein (hsp70) in regulating cellular response to heat shock was examined by using three closely re lated rat cells: control Rat-1 cells, thermotolerant Rat-1 (TT Rat-1) cells, and heat-resistant M21 cells, a derivative of Rat-1 cells that constitutively overexpress human hsp70, In all these cells, after a pr escribed heat shock, the level of the phosphorylated form of heat shoc k transcription factor HSF1 and that of HSF1 capable of binding to its cognitive DNA sequence heat shock element (HSE) exhibit similar time dependence. The amount of a constitutive HSE-binding activity (CHBA), on the other hand, inversely correlates with those of the two aforemen tioned forms of HSF1. The recovery kinetics from heat shock are differ ent for the three cell lines, with the thermal-resistant TT Rat-1 and M21 cells showing faster recovery in terms of the state of phosphoryla tion of HSF1 and its ability to bind HSE or in terms of the reappearan ce of CHBA. Treatment with okadaic acid, a serine/threonine phosphatas e inhibitor, delays the recovery kinetics of Rat-1 cells but not that of thermal-resistant M21 cells, These results are interpreted in terms of a role for hsp70 in the recovery of heat-shocked mammalian cells.