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XB-ART-57672
Life Sci Alliance January 1, 2021; 4 (2):

FAM83F regulates canonical Wnt signalling through an interaction with CK1α.

Dunbar K , Jones RA , Dingwell K , Macartney TJ , Smith JC , Sapkota GP .


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, whereas 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 GSK-3β because the attenuation of Wnt signalling caused by loss of FAM83F can be rescued by GSK-3 inhibition. Introduction of a farnesyl-deficient mutant of FAM83F in cells through CRISPR/Cas9 genome editing redirects the FAM83F-CK1α complex away from the plasma membrane and significantly attenuates Wnt signalling, indicating that FAM83F exerts its effects on Wnt signalling at the plasma membrane.

PubMed ID: 33361109
PMC ID: PMC7768192
Article link: Life Sci Alliance
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: axin2 csnk1a1 dld isyna1 psmd6 u2af1 wnt3a


Article Images: [+] show captions
References [+] :
Amit, Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway. 2002, Pubmed