THE ENDOPLASMIC RETICULAR HEAT-SHOCK PROTEIN GP96 IS TRANSCRIPTIONALLY UP-REGULATED IN INTERFERON-TREATED CELLS

A cDNA clone complementary to an interferon (IFN)-induced mRNA approxi mately 3 kb in length was identified and sequenced revealing homology with the endoplasmic reticular heat shock protein/ATPase gp96. Both IF N-alpha and -gamma transcriptionally upregulate expression of this gen e. gp96 transcripts, protein, and ATPase activity are shown to be enha nced as a result of IFN treatment in two human cell lines and-this eff ect requires de novo protein synthesis. gp96 molecules have recently b een implicated in the presentation of endogenous antigens. A number of the key elements in this pathway, the transporter proteins, the major histocompatibility complex (MHC)-linked units of the proteasomes and the MHC class I molecules are known to be IFN inducible. Our results s how that yet another molecule suggested to play an accessory role in t he endogenous presentation pathway is IFN inducible. Further, our stud ies represent the first demonstration of modulation of expression of a heat shock protein by a cytokine and identify a new enzymatic activit y upregulated in IFN-treated cells.