Department of Biology, University of Ioannina, Ioannina, Greece.
Int J Cancer. 2011 Apr 15;128(8):1989-95. doi: 10.1002/ijc.25510.
The p14(ARF) is a key tumor suppressor induced mainly by oncogenic stimuli. Although p14(ARF) does not seem to respond to DNA damage, there are very few data regarding its role in other forms of stress, such as heat shock (HS) and oxidative stress (OS). Here, we report that suppression of p14(ARF) increased resistance to cell death when cells were treated with H(2) O(2) or subjected to HS. In this setting, protection from cell death was mediated by elevated levels and activity of β-catenin, as downregulation of β-catenin alleviated the protective role of p14(ARF) silencing. Moreover, Hsp70 was shown to regulate β-catenin protein levels by interacting with p14(ARF) , suggesting that Hsp70, p14(ARF) and β-catenin form a regulatory network. This novel pathway triggers cell death signals when cells are exposed to HS and OS.
p14(ARF) 是一种主要由致癌刺激诱导的关键肿瘤抑制因子。尽管 p14(ARF) 似乎对 DNA 损伤没有反应，但关于其在其他形式的应激（如热休克 (HS) 和氧化应激 (OS)）中的作用的资料很少。在这里，我们报告说，当细胞用 H2O2 处理或受到 HS 时，抑制 p14(ARF) 会增加对细胞死亡的抵抗力。在这种情况下，β-连环蛋白水平和活性的升高介导了对细胞死亡的保护，因为下调β-连环蛋白减轻了 p14(ARF) 沉默的保护作用。此外，热休克蛋白 70 (Hsp70) 通过与 p14(ARF) 相互作用来调节 β-连环蛋白蛋白水平，表明 Hsp70、p14(ARF) 和 β-连环蛋白形成一个调节网络。当细胞暴露于 HS 和 OS 时，这条新途径会引发细胞死亡信号。
