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bioRxiv · 10.1101/2020.05.25.114504

FAM83F regulates canonical Wnt signalling through an interaction with CK1α

Dunbar, K.·Jones, R. A.·Dingwell, K. S.·Macartney, T.·Smith, J. C.·Sapkota, G. P.
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Abstract

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 CK1 at the plasma membrane. This interaction with CK1 is essential for FAM83F to activate Wnt signalling, and FAM83F mutants that do not interact with CK1 fail to induce axis duplication in Xenopus embryos and to activate Wnt signalling in cells. FAM83F acts upstream of the {beta}-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-CK1 complex to the nucleus and significantly attenuates Wnt signalling, indicating that FAM83F exerts its effects on Wnt signalling at the plasma membrane.

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Dunbar, K., Jones, R. A., Dingwell, K. S., Macartney, T., Smith, J. C., Sapkota, G. P.. 2020-05-26. FAM83F regulates canonical Wnt signalling through an interaction with CK1α. https://doi.org/10.1101/2020.05.25.114504

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