E1A signaling to p53 involves the p19<sup>ARF</sup>tumor suppressor
Elisa de Stanchina(St. Jude Children's Research Hospital), Mila E. McCurrach(St. Jude Children's Research Hospital), Frédérique Zindy(St. Jude Children's Research Hospital), Sheau-Yann Shieh(St. Jude Children's Research Hospital), Gerardo Ferbeyre(St. Jude Children's Research Hospital), Andrew V. Samuelson(St. Jude Children's Research Hospital), Carol Prives(St. Jude Children's Research Hospital), Martine F. Roussel(St. Jude Children's Research Hospital), Charles J. Sherr(St. Jude Children's Research Hospital), Scott Lowe(St. Jude Children's Research Hospital)
Cited by 610Open Access
Abstract
The adenovirus E1A oncogene activates p53 through a signaling pathway involving the retinoblastoma protein and the tumor suppressor p19(ARF). 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 p19(ARF) restores p53 accumulation and resensitizes ARF-null cells to apoptotic signals. Therefore, p19(ARF) functions as part of a p53-dependent failsafe mechanism to counter uncontrolled proliferation. Synergistic effects between the p19(ARF) and DNA damage pathways in inducing p53 may contribute to E1A's ability to enhance radio- and chemosensitivity.