Heat shock protein hsp70 protects cells from thermal stress even after deletion of its ATP-binding domain.

Retroviral-mediated gene transfer experiments show that rodent cells become heat resistant when stably and constitutively expressing a cloned human gene encoding an intact human 70-kDa heat shock protein (hsp70). Cells expressing higher levels of the hsp70 protein generally tolerate thermal stress better, whereas cells expressing either of two mutated hsp70-encoding genes, one with a 4-base pair out-of-frame deletion and one with an in-frame deletion of codons 438-618, are heat sensitive. These results provide strong evidence that expression of hsp70 leads directly to thermal tolerance. Surprisingly, cells expressing a mutant hsp70 of a human gene missing codons 120-428 are, nevertheless, heat resistant. Because the deleted region of this mutant contains the ATP-binding domain of human hsp70, this domain appears dispensable in the hsp70-mediated protection of cells from thermal stress.