E1A deregulates the centrosome cycle in a ran GTPase-dependent manner

Antonio De Luca, Rosamaria Mangiacasale, Anna Severino, Lorenzo Malquori, Alfonso Baldi, Antonella Palena, Anna Maria Mileo, Patrizia Lavia, Marco G. Paggi

Research output: Contribution to journalArticlepeer-review


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 NH2-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 NH2-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.

Original languageEnglish
Pages (from-to)1430-1437
Number of pages8
JournalCancer Research
Issue number6
Publication statusPublished - Mar 15 2003

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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