REPRESSION OF C-JUN-INDUCED MOUSE MAJOR HISTOCOMPATIBILITY CLASS-I PROMOTER (H-2K(B)) ACTIVITY BY THE ADENOVIRUS TYPE 12-UNIQUE 52R E1A PROTEIN

Down-regulation of major histocompatibility (MHC) class I gene express ion by protein products of the early region 1A (E1A), which might allo w transformed cells to escape the host immune system, is discussed as one cause for the oncogenicity of Adenovirus (Ad) subtype 12-transform ed cells, The MHC class I promoter is activated through several cellul ar transcription factors among them AP-1, whose target sequences are l ocated in the enhancers A and B, and NF kappa B, In this report we pre sent evidence that the Ad12-unique 52R E1A protein inhibits c-Jun-indu ced activation of MHC class I gene expression, Repression occurs throu gh both AP-1 recognition sequences with the AP-1 binding site of Enhan cer A, which can be bound by c-Jun dimers irt vitro, being the main ta rget for c-Jun activation as well as 52R-mediated down-regulation, Fur thermore our data revealed that both promoter elements of Enhancer A, the AP-1 and NF kappa B binding sites, are necessary for full promoter activity, As NF kappa B is down-regulated by the 266R protein of Ad12 E1A our results suggest a model in which two Ad12 E1A proteins co-ope rate in the repression of MHC class I gene expression.