E1A deregulates the centrosome cycle in a Ran GTPase-dependent manner.

By means of the yeast two-hybrid system, we have discovered a novel physical interaction between the adenovirus E1A oncoprotein and Ran, a small GTPase which regulates nucleocytoplasmic transport, cell cycle progression, and mitotic spindle organization. Expression of E1A elicits induction of S phase and centrosome amplification in a variety of ...
rodent cell lines. The induction of supernumerary centrosomes requires functional RCC1, the nucleotide exchange factor for Ran and, hence, a functional Ran network. The E1A portion responsible for the interaction with Ran is the extreme NH(2)-terminal region (amino acids 1-36), which is also required for the induction of centrosome amplification. In an in vitro assay with recombinant proteins, wild-type E1A interferes with nucleotide exchange on Ran, whereas an E1A mutant, deleted from the extreme NH(2)-terminal region, does not. In addition, we detected an in vitro interaction between Ran and HPV-16 E7 and SV40 large T antigen, two oncoproteins functionally related to E1A. These findings suggest a common pathway of these oncoproteins in eliciting virus-induced genomic instability.
Mesh Terms:
3T3 Cells, Adenovirus E1A Proteins, Animals, Antigens, Polyomavirus Transforming, Cell Cycle Proteins, Cell Line, Centrosome, Cricetinae, Guanine Nucleotide Exchange Factors, Hela Cells, Humans, Mice, Nuclear Proteins, Oncogene Proteins, Viral, S Phase, Subcellular Fractions, Transfection, ran GTP-Binding Protein
Cancer Res.
Date: Mar. 15, 2003
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