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E1A signaling to p53 involves the p19ARFtumor suppressor

E1A signaling to p53 involves the p19ARFtumor suppressor

Authors :
Sheau-Yann Shieh
Carol Prives
Elisa de Stanchina
Charles J. Sherr
Mila E. McCurrach
Frederique Zindy
Gerardo Ferbeyre
Andrew V. Samuelson
Martine F. Roussel
Scott W. Lowe
Source :
Genes & Development. 12:2434-2442
Publication Year :
1998
Publisher :
Cold Spring Harbor Laboratory, 1998.

Abstract

The adenovirus E1A oncogene activates p53 through a signaling pathway involving the retinoblastoma protein and the tumor suppressor p19ARF. The ability of E1A to induce p53 and its transcriptional targets is severely compromised in ARF-null cells, which remain resistant to apoptosis following serum depletion or adriamycin treatment. Reintroduction of p19ARF restores p53 accumulation and resensitizes ARF-null cells to apoptotic signals. Therefore, p19ARF functions as part of a p53-dependent failsafe mechanism to counter uncontrolled proliferation. Synergistic effects between the p19ARF and DNA damage pathways in inducing p53 may contribute to E1A’s ability to enhance radio- and chemosensitivity.

Details

ISSN :
15495477 and 08909369
Volume :
12
Database :
OpenAIRE
Journal :
Genes & Development
Accession number :
edsair.doi.dedup.....6bb62d1272ee7783fbe9c5da16fb0206
Full Text :
https://doi.org/10.1101/gad.12.15.2434