Ub and Dub of RNF43/ZNRF3 in the WNT signalling pathway.
Ub and Dub of RNF43/ZNRF3 in the WNT signalling pathway.
复制标题
WNT信号通路中RNF43/ZNRF3的Ub和Dub。
DOI：
10.15252/embr.202152970
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发表时间：
2021-05-05
期刊：
影响因子：
7.7
通讯作者：
Koo BK
中科院分区：
文献类型：
--
作者：
Colozza G;Koo BK
E3 泛素连接酶环指蛋白 43 (RNF43) 和锌环指 3 (ZNRF3) 因其在成体干细胞稳态过程中调节 WNT 信号传导的关键作用而受到极大关注。通过促进 WNT 受体的周转，Frizzled 和 LRP5/6、RNF43 和 ZNRF3 确保干细胞中维持适当的 WNT 活性水平。最近的几项研究开始揭示 RNF43/ZNRF3 活性的分子机制，但人们对 RNF43/ZNRF3 在翻译后水平的调控知之甚少。本期 EMBO 报告中的一项研究确定去泛素化酶 USP42 是 WNT 信号传导的关键调节因子，它通过拮抗 R-spondins 诱导的 RNF43/ZNRF3 泛素依赖性清除来发挥作用（Giebel 等人，2021）。本期的一项研究表明去泛素化酶 USP42 与 Wnt 信号传导有关。 USP42 稳定细胞表面的 RNF43/ZNRF3，导致 LRP6 和 Frizzled 的更新增加以及 Wnt 信号传导的抑制。
The E3 ubiquitin ligases RING finger protein 43 (RNF43) and zinc and RING finger 3 (ZNRF3) have received great attention for their critical role in regulating WNT signalling during adult stem cell homeostasis. By promoting the turnover of WNT receptors, Frizzled and LRP5/6, RNF43 and ZNRF3 ensure that proper levels of WNT activity are maintained in stem cells. The molecular mechanism of RNF43/ZNRF3 activity is beginning to emerge from several recent studies, yet little is known about the regulation of RNF43/ZNRF3 at the post‐translational level. A study in this issue of EMBO Reports identifies the deubiquitinating enzyme USP42 as a key regulator of WNT signalling, which acts by antagonizing the ubiquitin‐dependent clearance of RNF43/ZNRF3 induced by R‐spondins (Giebel et al, 2021). A study in this issue implicates the deubiquitinating enzyme USP42 in Wnt signalling. USP42 stabilizes RNF43/ZNRF3 at the cell surface, resulting in increased turnover of LRP6 and Frizzled and the inhibition of Wnt signalling.