How does USP8 turn on Smoothened?
USP8 deubiquitinates Smoothened, promoting Hh-dependent cell-surface accumulation and signaling while limiting early-endosome localization.
Source
USP8 promotes smoothened signaling by preventing its ubiquitination and changing its subcellular localization
Study at a glance
- Design
- Animal / in-vitro — RNAi screen of Drosophila DUBs in wings and S2 cells focused on USP8–Smo regulation
- N
- Drosophila genetics and S2 cell assays — no single sample N
- Population
- Drosophila tissues and S2 cells
- Outcome
- USP8 prevention of Smoothened ubiquitination promoting Hedgehog signaling
Structured fields used in claim comparison tables when every cited study has a complete layer.
Inspect source passages
How does USP8 turn on Smoothened?
These passages occur verbatim in the stored paper text. They support the points listed below; they do not verify every statement in the explanation.
What DUB prevents Smo ubiquitination?
By using an RNAi screen that targets Drosophila DUBs in both the wings and cultured S2 cells, we identified USP8 as a DUB that prevents Smo ubiquitination and enhances the signaling activity of the protein.
What is Smoothened’s role in Hh signaling?
The seven transmembrane protein Smoothened (Smo) acts as a signal transducer, and the activity of Smo is inhibited by Ptc in the absence of Hh –.
What they did
RNAi screen of Drosophila DUBs in wings and S2 cells, then tested USP8 effects on Smo ubiquitination, localization, and Hh responses.
What they found
USP8 prevents Smo ubiquitination and enhances signaling; Hh promotes Smo–USP8 interaction; USP8 is required for Hh-induced surface accumulation and keeps Smo out of Rab5 early endosomes.
The limits
What it doesn't show
Does not fully identify the ubiquitin ligase opposing USP8 on Smo in every tissue.
Key terms
- Smoothened (Smo)
- Seven-TM transducer of Hedgehog signaling.
- USP8
- Deubiquitinating enzyme that removes ubiquitin from substrates.
- Hedgehog (Hh)
- Morphogen pathway controlling growth and patterning.
- Deubiquitination
- Enzymatic removal of ubiquitin marks.
- Early endosome
- Rab5-positive compartment in the endocytic pathway.
Flashcards
0 of 11 answers reviewed
Research intelligence for this paper
See its role on concept claims, tensions it is part of, placement history, and related discoveries.
Quiz yourself
USP8’s effect on Smo:
Common questions
What does USP8 do to Smo?
Prevents ubiquitination and enhances signaling.
Where does Hh drive Smo?
Cell-surface accumulation.
Where does USP8 keep Smo from going?
Rab5-labeled early endosomes.
System?
Drosophila wings and S2 cells.
More on Cell signalling