THE INTERFERON-INDUCIBLE MURINE P48 (ISGF3-GAMMA) GENE IS REGULATED BY PROTOONCOGENE C-MYC

p48 protein is an integral component of the multimeric interferon (IFN )-regulated transcription factor, ISGF3. We have shown earlier that th is gene is regulated by a novel IFN-gamma-regulated element. In additi on to the IFN-regulated element, a myc-max binding site is also presen t in this promoter. In this investigation we have studied the role of this site in the regulation of the p48 gene. In serum-induced quiescen t cells Myc up-regulated the expression of p48 mRNA. We show that the protooncogene Myc regulates the expression of p48 through the element CACGTG. Mutations in this motif abolish Myc-inducibility of the report er genes carrying p48 promoter elements. Purified Myc and Max proteins interact with the Myc-stimulated element of the p48 promoter. We also show that cells lacking p48 expression are highly susceptible to the cytocidal action of anticancer drugs. Taken together these data sugges t that p48 may function as an anti-stress cell survival factor.