The function of the FAM83F protein, like the functions of many members of the FAM83 family, is poorly understood. Here we show that injection of Fam83f mRNA into Xenopus embryos causes axis duplication, a phenotype indicative of enhanced Wnt signalling. Consistent with this, overexpression of FAM83F activates Wnt signalling, whilst ablation of FAM83F from human colorectal cancer (CRC) cells attenuates it. We demonstrate that FAM83F is farnesylated and interacts and co-localises with CK1α at the plasma membrane. This interaction with CK1α is essential for FAM83F to activate Wnt signalling, and FAM83F mutants that do not interact with CK1α fail to induce axis duplication in Xenopus embryos and to activate Wnt signalling in cells. FAM83F acts upstream of the β-catenin destruction complex, because the attenuation of Wnt signalling caused by loss of FAM83F can be rescued by GSK-3 inhibition. Introduction of a farnesyl-deficient mutant mis-localises the FAM83F-CK1α complex to the nucleus and significantly attenuates Wnt signalling, indicating that FAM83F exerts its effects on Wnt signalling at the plasma membrane.

中文翻译：

---

FAM83F通过与CK1α的相互作用调节经典Wnt信号传导

FAM83F蛋白的功能，就像FAM83家族的许多成员的功能，了解甚少。在这里，我们显示将Fam83f mRNA注入非洲爪蟾胚胎会导致轴重复，这是一种指示Wnt信号增强的表型。与此相一致，FAM83F的过表达激活Wnt信号传导，而人结肠直肠癌细胞（CRC）切除FAM83F则使其减弱。我们证明，FAM83F是法尼基化的，并且与质膜上的CK1α相互作用且共定位。与CK1α的这种相互作用对于FAM83F激活Wnt信号是必不可少的，并且不与CK1α相互作用的FAM83F突变体无法在非洲爪蟾胚胎中诱导轴重复并不能激活细胞中的Wnt信号。FAM83F在β-catenin破坏复合体的上游起作用，因为可以通过GSK-3抑制来挽救由FAM83F缺失引起的Wnt信号减弱。法呢基缺陷型突变体的引入将FAM83F-CK1α复合物错误定位在细胞核上，并显着减弱Wnt信号传导，表明FAM83F对质膜上的Wnt信号传导发挥作用。