Interaction between a Cellular Protein That Binds to the C-terminal Region of Adenovirus E1A (CtBP) and a Novel Cellular Protein Is Disrupted by E1A through a Conserved PLDLS Motif

• Published in: The Journal of biological chemistry Vol. 273; no. 15; pp. 8549 - 8552
• Main Authors: Schaeper, Ute, Subramanian, T., Lim, Louis, Boyd, Janice M., Chinnadurai, G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10-04-1998; American Society for Biochemistry and Molecular Biology
• Subjects: Adenovirus E1A Proteins - chemistry; Adenovirus E1A Proteins - genetics; Adenovirus E1A Proteins - metabolism; Adenoviruses, Human - metabolism; Amino Acid Sequence; Base Sequence; Binding Sites; Cell Transformation, Neoplastic; Conserved Sequence; Exons; Genes, ras; HeLa Cells; Humans; Molecular Sequence Data; Recombinant Fusion Proteins - biosynthesis; Recombinant Fusion Proteins - metabolism; Sequence Alignment; Sequence Homology, Amino Acid; Transfection
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.273.15.8549

Adenovirus E1A proteins immortalize primary animal cells and cooperate with several other oncogenes in oncogenic transformation. These activities are primarily determined by the N-terminal half (exon 1) of E1A. Although the C-terminal half (exon 2) is also essential for some of these activities, it is dispensable for cooperative transformation with the activated T24 rasoncogene. Exon 2 negatively modulates in vitrocooperative transformation with T24 ras as well as the tumorigenic and metastatic potentials of transformed cells. A short C-terminal sequence of E1A governs the oncogenesis-restraining activity of exon 2. This region of E1A binds with a cellular phosphoprotein, CtBP, through a 5-amino acid motif, PLDLS, conserved among the E1A proteins of human adenoviruses. To understand the mechanism by which interaction between E1A and CtBP results in tumorigenesis-restraining activity, we searched for cellular proteins that complex with CtBP. Here, we report the cloning and characterization of a 125-kDa protein, CtIP, that binds with CtBP through the PLDLS motif. E1A exon 2 peptides that contain the PLDLS motif disrupt the CtBP-CtIP complex. Our results suggest that the tumorigenesis-restraining activity of E1A exon 2 may be related to the disruption of the CtBP-CtIP complex through the PLDLS motif.