Modulation of oncogenic transformation by the human adenovirus E1A C-terminal region.
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.
Chinnadurai
G
G
Institute for Molecular Virology, Saint Louis University School of Medicine, 3681 Park Ave., St. Louis, MO 63110, USA. Chinnag@slu.edu
D017500:Adenovirus E1A Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000260:Adenoviruses, Human / Q000378:metabolism*; D000429:Alcohol Oxidoreductases; D002472:Cell Transformation, Viral / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D010750:Phosphoproteins / Q000378:metabolism / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology
D017500:Adenovirus E1A Proteins; D004268:DNA-Binding Proteins; D010750:Phosphoproteins; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein