The Adenovirus E1A-associated 300-kD Protein Exhibits Properties of a Transcriptional Coactivator and Belongs to an Evolutionarily Conserved Family (original) (raw)

1. R. Eckner,
2. Z. Arany,
3. M. Ewen,
4. W. Sellers, and
5. D.M. Livingston
6. Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115

Excerpt

The development of a tumorigenic phenotype in a previously untransformed cell is a multistep process requiring both the activation of oncogenes and the inactivation of tumor suppressor genes (Fearon and Vogelstein 1990; Scrable et al. 1990). The E1A and E1B proteins encoded by the early region of adenovirus can elicit a tumorigenic phenotype and have provided insights into the interplay between the products of DNA tumor viral oncogenes and certain tumor suppressor genes. The study of these two viral genes has also helped to elucidate the phenomenon of cooperativity among certain oncogenes (Ruley 1983).

The two major E1A polypeptides are synthesized from alternatively spliced transcripts and are designated 12S and 13S E1A mRNA products. Both proteins display transforming activity in the presence of E1B. The oncogenic activity of E1A is tightly linked to its ability to bind to a set of cellular proteins. These proteins recognize discrete E1A regions that...