Wingless and Archipelago, a fly E3 ubiquitin ligase and a homolog of human tumor suppressor FBW7, show an antagonistic relationship in wing development

Cited 2 time in webofscience Cited 0 time in scopus
  • Hit : 228
  • Download : 34
Background Archipelago (Ago) is aDrosophilahomolog of mammalian F-box and WD repeat domain-containing 7 (FBW7, also known as FBXW7). In previous studies, FBW7 has been addressed as a tumor suppressor mediating ubiquitin-dependent proteolysis of several oncogenic proteins. Ubiquitination is a type of protein modification that directs protein for degradation as well as sorting. The level of beta-catenin (beta-cat), an intracellular signal transducer in Wnt signaling pathway, is reduced upon overexpression of FBW7 in human cancer cell lines. Loss of function mutations in FBW7 and overactive Wnt signaling have been reported to be responsible for human cancers. Results We found that Ago is important for the formation of shafts in chemosensory bristles at wing margin. This loss of shaft phenotype by knockdown ofagowas rescued by knockdown ofwingless(wg) whereas wing notching phenotype by knockdown ofwgwas rescued by knockdown ofago, establishing an antagonistic relationship betweenagoandwg.In line with this finding, knockdown ofagoincreased the level of Armadillo (Arm), a homolog of beta-cat, inDrosophilatissue. Furthermore, knockdown ofagoincreased the level of Distal-less (Dll) and extracellular Wg in wing discs. In S2 cells, the amount of secreted Wg was increased by knockdown of Ago but decreased by Ago overexpression. Therefore, Ago plays a previously unidentified role in the inhibition of Wg secretion. Ago-overexpressing clones in wing discs exhibited accumulation of Wg in endoplasmic reticulum (ER), suggesting that Ago prevents Wg protein from moving to Golgi from ER. Conclusions We concluded that Ago plays dual roles in inhibiting Wg signaling. First, Ago decreases the level of Arm, by which Wg signaling is downregulated in Wg-responding cells. Second, Ago decreases the level of extracellular Wg by inhibiting movement of Wg from ER to Golgi in Wg-producing cells.
Publisher
BMC
Issue Date
2020-07
Language
English
Article Type
Article
Citation

BMC DEVELOPMENTAL BIOLOGY, v.20, no.1

ISSN
1471-213X
DOI
10.1186/s12861-020-00217-1
URI
http://hdl.handle.net/10203/275564
Appears in Collection
BS-Journal Papers(저널논문)
Files in This Item
Nam_et_al-2020-BMC_Developmental_Biology.pdf(4.62 MB)Download
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 2 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0