Np95 is regulated by E1A during mitotic reactivation of terminally differentiated cells and is essential for S phase entry

Ian Marc Bonapace, Lucia Latella, Roberto Papait, Francesco Nicassio, Alessandra Sacco, Masahiro Muto, Marco Crescenzi, Pier Paolo Di Fiore

Research output: Contribution to journalArticle

Abstract

Terminal differentiation exerts a remarkably tight control on cell proliferation. However, the oncogenic products of DNA tumor viruses, such as adenovirus E1A, can force postmitotic cells to proliferate, thus representing a powerful tool to study progression into S phase. In this study, we identified the gene encoding Np95, a murine nuclear phosphoprotein, as an early target of E1A-induced transcriptional events. In terminally differentiated (TD) cells, the activation of Np95 was specifically induced by E1A, but not by overexpression of E2F-1 or of the cyclin E (cycE)-cyclin-dependent kinase 2 (cdk2) complex. In addition, the concomitant expression of Np95 and of cycE-cdk2 was alone sufficient to induce S phase in TD cells. In NIH-3T3 cells, the expression of Np95 was tightly regulated during the cell cycle, and its functional ablation resulted in abrogation of DNA synthesis. Thus, expression of Np95 is essential for S phase entry. Previous evidence suggested that E1A, in addition to its well characterized effects on the pRb/E2F-1 pathway, activates a parallel and complementary pathway that is also required for the reentry in S phase of TD cells (Tiainen, M., D. Spitkousky, P. Jansen-Dürr, A. Sacchi, and M. Crescenzi. 1996. Mol. Cell. Biol. 16:5302-5312). From our results, Np95 appears to possess all the characteristics to represent the first molecular determinant identified in this pathway.

Original languageEnglish
Pages (from-to)909-914
Number of pages6
JournalJournal of Cell Biology
Volume157
Issue number6
DOIs
Publication statusPublished - Jun 10 2002

Keywords

  • Cell cycle
  • CycE-cdk2
  • E1A
  • Np95
  • PRb

ASJC Scopus subject areas

  • Cell Biology

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