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

73 Citations (Scopus)

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

Fingerprint

S Phase
Cyclin-Dependent Kinase 2
Cyclin E
DNA Tumor Viruses
NIH 3T3 Cells
Phosphoproteins
Adenoviridae
Cell Cycle
Cell Proliferation
DNA
Genes

Keywords

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

ASJC Scopus subject areas

  • Cell Biology

Cite this

Np95 is regulated by E1A during mitotic reactivation of terminally differentiated cells and is essential for S phase entry. / Bonapace, Ian Marc; Latella, Lucia; Papait, Roberto; Nicassio, Francesco; Sacco, Alessandra; Muto, Masahiro; Crescenzi, Marco; Di Fiore, Pier Paolo.

In: Journal of Cell Biology, Vol. 157, No. 6, 10.06.2002, p. 909-914.

Research output: Contribution to journalArticle

Bonapace, Ian Marc ; Latella, Lucia ; Papait, Roberto ; Nicassio, Francesco ; Sacco, Alessandra ; Muto, Masahiro ; Crescenzi, Marco ; Di Fiore, Pier Paolo. / Np95 is regulated by E1A during mitotic reactivation of terminally differentiated cells and is essential for S phase entry. In: Journal of Cell Biology. 2002 ; Vol. 157, No. 6. pp. 909-914.
@article{6b4a6d3584e143819e0122a966ddcd6e,
title = "Np95 is regulated by E1A during mitotic reactivation of terminally differentiated cells and is essential for S phase entry",
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-D{\"u}rr, 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.",
keywords = "Cell cycle, CycE-cdk2, E1A, Np95, PRb",
author = "Bonapace, {Ian Marc} and Lucia Latella and Roberto Papait and Francesco Nicassio and Alessandra Sacco and Masahiro Muto and Marco Crescenzi and {Di Fiore}, {Pier Paolo}",
year = "2002",
month = "6",
day = "10",
doi = "10.1083/jcb.200201025",
language = "English",
volume = "157",
pages = "909--914",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "6",

}

TY - JOUR

T1 - Np95 is regulated by E1A during mitotic reactivation of terminally differentiated cells and is essential for S phase entry

AU - Bonapace, Ian Marc

AU - Latella, Lucia

AU - Papait, Roberto

AU - Nicassio, Francesco

AU - Sacco, Alessandra

AU - Muto, Masahiro

AU - Crescenzi, Marco

AU - Di Fiore, Pier Paolo

PY - 2002/6/10

Y1 - 2002/6/10

N2 - 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.

AB - 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.

KW - Cell cycle

KW - CycE-cdk2

KW - E1A

KW - Np95

KW - PRb

UR - http://www.scopus.com/inward/record.url?scp=0037054539&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037054539&partnerID=8YFLogxK

U2 - 10.1083/jcb.200201025

DO - 10.1083/jcb.200201025

M3 - Article

C2 - 12058012

AN - SCOPUS:0037054539

VL - 157

SP - 909

EP - 914

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 6

ER -