Relationship between the transforming and transcriptional regulatory functions of adenovirus 2 E1a oncogene.

The E1a region of adenoviruses encodes two early proteins of 289 amino acids (289R) and 243R from two differentially spliced mRNAs of 13 and 12 S, respectively. These E1a proteins of adenoviruses are multifunctional and have been shown to play an essential role in cellular immortalization and transformation. The E1a gene is also known to regulate the expression of certain viral and cellular genes in a positive or negative manner. To identify the domains of the E1a proteins required for their transformation and transcriptional regulatory functions, we have constructed and analyzed several E1a mutations. A region located between amino acid residues 125 and 127 appears to be essential for cell transformation in cooperation with both E1b and the activated cellular oncogene, T24 Har-ras. Mutation at this region does not affect the ability of E1a to trans-activate the Ad2 early E2 promoter significantly. Our experiments have not revealed the domain of E1a most essential for trans-repression. However, the region between amino acid residues 125 and 127 appears to have a small effect on E1a-mediated repression of the immunoglobulin heavy-chain and polyoma enhancers but has no significant effect on the SV40 enhancer. From our results, it appears that the transformation function of E1a can be dissociated from its transcriptional regulatory functions.