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
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
Want these cards to stick?
Save the deck to NoteFren and study it with spaced repetition.
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