Simultaneous hyperactivation of Wnt and antioxidant response (AR) are often observed during oncogenesis. However, it remains unclear how the β-catenin-driven Wnt and the Nrf2-driven AR mutually regulate each other. The situation is compounded because many players in these two pathways are redox sensors, rendering bolus redox signal-dosing methods uninformative. Herein we examine the ramifications of single-protein target-specific AR upregulation in various knockdown lines. Our data document that Nrf2/AR strongly inhibits β-catenin/Wnt. The magnitude and mechanism of this negative regulation are dependent on the direct interaction between β-catenin N terminus and β-TrCP1 (an antagonist of both Nrf2 and β-catenin), and independent of binding between Nrf2 and β-TrCP1. Intriguingly, β-catenin positively regulates AR. Because AR is a negative regulator of Wnt regardless of β-catenin N terminus, this switch of function is likely sufficient to establish a new Wnt/AR equilibrium during tumorigenesis.

中文翻译：

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β-TrCP1是Wnt信号的波动性调节剂

通常在致癌过程中观察到Wnt同时过度活化和抗氧化反应（AR）。但是，尚不清楚β-连环蛋白驱动的Wnt和Nrf2驱动的AR如何相互调节。由于这两个途径中的许多参与者都是氧化还原传感器，因此情况变得更加复杂，从而使大剂量氧化还原信号剂量分配方法变得无用。在本文中，我们研究了各种击倒系中单蛋白靶标特异性AR上调的影响。我们的数据证明Nrf2 / AR强烈抑制β-catenin/ Wnt。这种负调控的强度和机制取决于β-cateninN末端与β-TrCP1（Nrf2和β-catenin的拮抗剂）之间的直接相互作用，并且独立于Nrf2与β-TrCP1之间的结合。有趣的是，β-连环蛋白正调控AR。