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.
Yang
S H
SH
Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Nussenzweig
A
A
Yang
W H
WH
Kim
D
D
Li
G C
GC
D000595:Amino Acid Sequence; D000818:Animals; D034961:Antigens, Nuclear; D001324:Autoantigens / Q000502:physiology*; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D000076249:Heat Shock Transcription Factors; D000072200:Ku Autoantigen; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D051381:Rats; D014157:Transcription Factors
D034961:Antigens, Nuclear; D001324:Autoantigens; D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; D004247:DNA; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; C000606511:Xrcc6 protein, rat; D000072200:Ku Autoantigen