Structure of two adenovirus type 12 transforming polypeptides and their evolutionary implications

Abstract

The human adenoviruses are classified according to their nucleotide sequence homology and their oncogenic potential in rodents^1,2. The left-hand end of the genome of the adenovirus types 5 (ad5), 7 (ad7) and 12 (ad12), which are respectively, non-oncogenic (subgroup C), weakly oncogenic (subgroup B) and highly oncogenic (subgroup A)^3–5, contains all the genetic information needed to induce and maintain the transformed phenotype. This part of the genome contains the early transcription unit designated E₁ which is subdivided into two transcription units E₁A and E₁B⁶. Two spliced mRNAs are transcribed from the E₁A region which codes for several phos-phorylated polypeptides. These polypeptides play a key role by controlling the expression of the other early transcription units^7,8. The major role of region E₁A in adenovirus cell transformation might be to activate the true transforming genes of the region E₁B. An additional role probably consists of the activation of some cellular genes as a restriction fragment containing this region can immortalize rodent cells in vitro. An important question is why some adenoviruses are oncogenic and others are not. We report here differences in the structures of the E₁A polypeptides from ad7 and adl2, compared to ad5, which may partially account for their differing oncogenicity.