E1A signaling to p53 involves the p19ARF tumor suppressor
E1A signaling to p53 involves the p19ARF tumor suppressor
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DOI：
10.1101/gad.12.15.2434
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发表时间：
1998-08-01
影响因子：
10.5
通讯作者：
Lowe, SW
中科院分区：
文献类型：
--
作者：
de Stanchina, E;McCurrach, ME;Lowe, SW
腺病毒E1a癌基因通过涉及视网膜母细胞瘤蛋白和肿瘤抑制因子p19(ARF)的信号通路激活P53。在ARF阴性细胞中，E1a诱导p53及其转录靶点的能力严重受损，这些细胞在血清耗尽或阿霉素处理后仍对凋亡具有抵抗力。P19(ARF)的重新引入恢复了P53的积聚，并使ARF缺失的细胞对凋亡信号重新敏感。因此，p19ARF作为p53依赖的失效安全机制的一部分来对抗失控的增殖。P19A-RF和DNA损伤通路在诱导p53过程中的协同作用可能有助于EIA增强放射和化疗敏感性。
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, p19ARF functions as part of a p53-dependent failsafe mechanism to counter uncontrolled proliferation. Synergistic effects between the p19A-RF and DNA damage pathways in inducing p53 may contribute to EIA's ability to enhance radio- and chemosensitivity.