E1A Oncogene of Adenovirus-12 Mediates Trans-repression of MHC Class I Transcription in Ad5/Ad12 Somatic Hybrid Transformed Cells

Abstract

Reduction of the Major Histocompatibility Complex (MHC) class I antigens on the surface of adenovirus type 12 (Ad12) transformed cells is thought to contribute to their tumorigenic potential. The E1A gene of Ad12 mediates this effect by repressing the MHC class I transcriptional enhancer. By contrast, Ad5-transformed cells are not blocked in class I gene expression and are nontumorigenic. Because E1A proteins modulate transcription by interacting with several different cellular factors. we inquired whether the Ad5 E1A proteins could interfere with the ability of Ad12 E1A proteins to repress class I transcription. Somatic cell hybrids, produced by fusing Ad5- and Ad12-transformed cells, expressed E1A proteins of both virus serotypes. The level of class I expression and transcription in the 5/12 hybrid cell lines was reduced to the same degree as in the original Ad12-transformed cells. Also observed in the 5/12 hybrid cell lines was strong binding activity to the R2 subelement of the H-2 class I enhancer which, in Ad12-transformed cells, correlates with repression of class I transcription. These results demonstrate that Ad12 E1A proteins mediate repression of the class I enhancer through a mechanism that is unaffected by Ad5 E1A proteins.