FAM83F regulates canonical Wnt signalling through an interaction with CK1α

Dunbar, Karen; Jones, Rebecca A.; Dingwell, Kevin S.; Macartney, Thomas; Smith, James C.; Sapkota, Gopal P.

doi:10.26508/lsa.202000805

Cited by 7 publications

(12 citation statements)

References 35 publications

(43 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As reported by Wang G et al, FAM83A has been confirmed to be highly expressed in lung adenocarcinoma and is associated with a poor prognosis (24). FAM83B inhibits cisplatin resistance in ovarian cancer by inhibiting the Wnt pathway (25), and high FAM83F expression plays a pro-oncogenic role in papillary thyroid cancer (26). The role of FAM83D in the occurrence and development of malignant tumours has also been preliminarily studied; FAM83A, FAM83C, FAM83D and FAM83E promote human mammary epithelial cell (HMEC) transformation (27).…”

Section: Discussionmentioning

confidence: 81%

YTHDF2 Inhibits the Migration and Invasion of Lung Adenocarcinoma by Negatively Regulating the FAM83D-TGFβ1-SMAD2/3 Pathway

et al. 2022

View full text Add to dashboard Cite

ObjectiveYTH domain family 2 (YTHDF2) is an important N6-methyladenosine (m6A) reader, but its role in lung adenocarcinoma remains elusive. This study assessed its function in lung adenocarcinoma.MethodsYTHDF2 expression in lung adenocarcinoma was explored using public databases, such as The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumour Analysis Consortium (CPTAC). The effect of YTHDF2 on a lung adenocarcinoma cell line was explored by performing cytological and molecular experiments. Molecules downstream of YTHDF2 were identified using proteomics, and the related pathways were verified through cytological and molecular biology experiments.ResultsYTHDF2 expression was upregulated in lung adenocarcinoma, and patients with high YTHDF2 expression experienced prolonged overall survival. In two lung cancer cell lines, YTHDF2 knockdown inhibited proliferation but promoted migration, invasion, and the epithelial-mesenchymal transition. The proteomic analysis identified 142 molecules downstream of YTHDF2, and 11 were closely related to survival. Further experiments revealed that YTHDF2 inhibited expression of the family with sequence similarity 83D (FAM83D)-TGFβ1-SMAD2/3 pathway components. This study is the first to show that YTHDF2 regulated the downstream TGFβ1-SMAD2/3 pathway through FAM83D in lung adenocarcinoma.ConclusionYTHDF2 inhibits the migration and invasion of lung adenocarcinoma cells by regulating the FAM83D-TGFβ1-pSMAD2/3 pathway, which may play an important role in lung cancer metastasis.

show abstract

Section: Discussionmentioning

confidence: 81%

YTHDF2 Inhibits the Migration and Invasion of Lung Adenocarcinoma by Negatively Regulating the FAM83D-TGFβ1-SMAD2/3 Pathway

et al. 2022

View full text Add to dashboard Cite

show abstract

“…CkIα has also been shown to be present in the nucleus in flies and vertebrates, where it has been implicated in the DNA damage response and nuclear organization ( 58 – 61 ). Moreover, CkIα nuclear protein interactions have been shown to be important in modulating both Wnt activity ( 62 ) and the nuclear entry of transcriptional regulators ( 63 ) and influence wg transcription ( 34 ).…”

Section: Discussionmentioning

confidence: 99%

Loss of IRF2BPL impairs neuronal maintenance through excess Wnt signaling

et al. 2022

View full text Add to dashboard Cite

De novo truncations in Interferon Regulatory Factor 2 Binding Protein Like ( IRF2BPL ) lead to severe childhood-onset neurodegenerative disorders. To determine how loss of IRF2BPL causes neural dysfunction, we examined its function in Drosophila and zebrafish. Overexpression of either IRF2BPL or Pits , the Drosophila ortholog, represses Wnt transcription in flies. In contrast, neuronal depletion of Pits leads to increased wingless ( wg ) levels in the brain and is associated with axonal loss, whereas inhibition of Wg signaling is neuroprotective. Moreover, increased neuronal expression of wg in flies is sufficient to cause age-dependent axonal loss, similar to reduction of Pits. Loss of irf2bpl in zebrafish also causes neurological defects with an associated increase in wnt1 transcription and downstream signaling. WNT1 is also increased in patient-derived astrocytes, and pharmacological inhibition of Wnt suppresses the neurological phenotypes. Last, IRF2BPL and the Wnt antagonist, CKIα, physically and genetically interact, showing that IRF2BPL and CkIα antagonize Wnt transcription and signaling.

show abstract

“…Embryos were then counted and scored for secondary axial phenotype classes as previously described (Dunbar et al, 2020).…”

Section: Animal Housing Husbandry and Microinjectionmentioning

confidence: 99%

Zebrafish reveal new roles for Fam83f in hatching and the DNA damage-mediated autophagic response

Jones,

Cooper,

Kelly

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

The FAM83 (Family with sequence similarity 83) family is highly conserved in vertebrates, but little is known of the functions of these proteins beyond their association with oncogenesis. Of the family, FAM83F is of particular interest because it is the only membrane-targeted FAM83 protein. When over-expressed, FAM83F activates the canonical Wnt signalling pathway and binds to and stabilizes p53; it therefore interacts with two pathways often dysregulated in disease. Insights into gene function can often be gained by studying the roles they play during development, and here we report the generation offam83fknock-out (KO) zebrafish, which we have used to study the role of Fam83f in vivo. We show that endogenousfam83fis most strongly expressed in the hatching gland of developing zebrafish embryos, and thatfam83fKO embryos hatch earlier than their wild-type (WT) counterparts, despite developing at a comparable rate. We also demonstrate thatfam83fKO embryos are more sensitive to ionizing radiation than WT embryos, an unexpected finding, bearing in mind the previously-reported ability of FAM83F to stabilize p53. Transcriptomic analysis shows that loss offam83fleads to downregulation of phosphatidylinositol-3-phosphate (PI(3)P) binding proteins and impairment of cellular degradation pathways, particularly autophagy, a crucial component of the DNA damage response. Finally, we show that Fam83f protein is itself targeted to the lysosome when over-expressed in HEK293T cells, and that this localization is dependent upon a C terminal signal sequence. The zebrafish lines we have generated suggest that Fam83f plays an important role in autophagic/lysosomal processes, resulting in dysregulated hatching and increased sensitivity to genotoxic stress in vivo.

show abstract

FAM83F regulates canonical Wnt signalling through an interaction with CK1α

Cited by 7 publications

References 35 publications

YTHDF2 Inhibits the Migration and Invasion of Lung Adenocarcinoma by Negatively Regulating the FAM83D-TGFβ1-SMAD2/3 Pathway

YTHDF2 Inhibits the Migration and Invasion of Lung Adenocarcinoma by Negatively Regulating the FAM83D-TGFβ1-SMAD2/3 Pathway

Loss of IRF2BPL impairs neuronal maintenance through excess Wnt signaling

Zebrafish reveal new roles for Fam83f in hatching and the DNA damage-mediated autophagic response

Contact Info

Product

Resources

About