How does USP8 turn on Smoothened?

USP8 deubiquitinates Smoothened, promoting Hh-dependent cell-surface accumulation and signaling while limiting early-endosome localization.

Keep what you just learned

Save these 11 cards to your NoteFren library. Your first review starts right away, and each card links back to the study it came from.

What DUB prevents Smo ubiquitination?

USP8.

What is Smoothened’s role in Hh signaling?

Seven-TM signal transducer inhibited by Patched without Hh.

How does Hh relate to USP8 and Smo?

Hh promotes Smo–USP8 interaction; USP8 is required for Hh-induced surface accumulation.

Where does USP8 prevent Smo from localizing?

Rab5-labeled early endosomes.

What happens if USP8 is inactivated?

Smo ubiquitination increases and Smo accumulation is prevented in wing discs.

What does USP8 overexpression do to Smo ubiquitin?

Down-regulates Smo ubiquitination and increases Smo accumulation.

What regulatory logic do authors propose for Smo?

Ubiquitination negatively regulates Smo; USP8 opposes that.

Where is Smo enriched when Hh is present in discs?

Plasma membrane of posterior-compartment cells receiving Hh.

Screen approach?

RNAi against Drosophila DUBs in wings and S2 cells.

Best topic takeaway?

Deubiquitination can promote cell-surface receptor/transducer signaling.

Does Hh only regulate Ci ubiquitination historically?

Prior work emphasized Ci; this paper extends ubiquitin control to Smo.