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E1A signaling to p53 involves the p19 ARF tumor suppressor

1998; Cold Spring Harbor Laboratory Press; Volume: 12; Issue: 15 Linguagem: Inglês

10.1101/gad.12.15.2434

1549-5477

Elisa de Stanchina, Mila E. McCurrach, Frédérique Zindy, Sheau-Yann Shieh, Gerardo Ferbeyre, Andrew V. Samuelson, Carol Prives, Martine F. Roussel, Charles J. Sherr, Scott Lowe,

Cancer Research and Treatments

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.