Cloning and characterization of rat Ku70: involvement of Ku autoantigen in the heat-shock response.

To study the role of the Ku autoantigen in the heat-shock response, we have cloned the 70-kDa subunit (the DNA-binding component of Ku) from a rat cDNA library. The deduced amino acid sequence of rat Ku70 bears extensive homology with the human and murine counterpart (83 and 97% identity, respectively). Overexpression of Ku70 in rat fibroblasts results in the specific repression of hsp-70 upon heat shock. The inhibition of induction of hsp-70 was greatest in cells expressing the highest level of Ku70. Induction of other heat-shock proteins besides hsp-70 by hyperthermia appears normal, as does the activation of the heat-shock transcription factor, HSF-1. It is likely that other factors besides HSF-1 are involved in controlling heat-shock gene transcription. While the formation of the Ku70 and Ku80 complex is important for repair of DNA double-strand breaks our data suggest that the 70-kDa subunit of Ku plays a role in regulating hsp-70 expression.