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Modulation of oncogenic transformation by the human adenovirus E1A C-terminal region.

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Institute for Molecular Virology, Saint Louis University School of Medicine, 3681 Park Ave., St. Louis, MO 63110, USA.


The E1A oncogene of human adenoviruses cooperates with other viral and cellular oncogenes in oncogenic transformation of primary and established cells. The N-terminal half of E1A proteins that form specific protein complexes with pRb family and p300/CBP transcriptional regulators is essential for the transforming activities of E1A. Although the C-terminal half of E1A is dispensable for the transforming activities, it negatively modulates the oncogenic activities of the N-terminal region. Mutants of E1A lacking the C-terminal half or a short C-terminal region exhibit a hyper-transforming phenotype in cooperative transformation assays with the activated ras oncogene. The E1A C-terminal region implicated in the oncogenesis-restraining activity interacts with a 48-kDa cellular phosphoprotein, CtBP, that functions as a transcriptional corepressor. It appears that the C-terminal region of E1A may suppress E1A-mediated oncogenic transformation by a dual mechanism of relieving repression cellular genes by CtBP, and also by antagonizing the oncogenic activities of the N-terminal half of E1A.

[Indexed for MEDLINE]

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