The Wnt β-catenin signaling pathway is a highly conserved mechanism that plays a critical role from embryonic development and adult stem cell homeostasis. However, dysregulation of the Wnt pathway has been implicated in various diseases, including cancer. Therefore, multiple layers of regulatory mechanisms tightly control the activation and suppression of the Wnt signal. The E3 ubiquitin ligases RNF43 and ZNRF3, which are known negative regulators of the Wnt pathway, are critical component of Wnt signaling regulation. These E3 ubiquitin ligases control Wnt signaling by targeting the Wnt receptor Frizzled to induce ubiquitination-mediated endo-lysosomal degradation, thus controlling the activation of the Wnt signaling pathway. We also discuss the regulatory mechanisms, interactors, and evolution of RNF43 and ZNRF3. This review article summarizes recent findings on RNF43 and ZNRF3 and their potential implications for the development of therapeutic strategies to target the Wnt signaling pathway in various diseases, including cancer.

中文翻译：

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Wnt 信号传导中的 RNF43 和 ZNRF3 - 膜上的主调节器。

Wnt β-连环蛋白信号通路是一种高度保守的机制，在胚胎发育和成体干细胞稳态中发挥着关键作用。然而，Wnt 通路的失调与多种疾病有关，包括癌症。因此，多层调控机制严格控制Wnt信号的激活和抑制。E3 泛素连接酶 RNF43 和 ZNRF3 是 Wnt 通路的已知负调节因子，是 Wnt 信号传导调节的关键组成部分。这些E3泛素连接酶通过靶向Wnt受体Frizzled诱导泛素化介导的内溶酶体降解来控制Wnt信号传导，从而控制Wnt信号传导途径的激活。我们还讨论了 RNF43 和 ZNRF3 的调控机制、相互作用因子和进化。这篇综述文章总结了 RNF43 和 ZNRF3 的最新发现，及其对开发针对包括癌症在内的多种疾病中 Wnt 信号通路的治疗策略的潜在影响。