The centrosomal deubiquitylase USP21 regulates Gli1 transcriptional activity and stability.
J Cell Sci
; 129(21): 4001-4013, 2016 11 01.
Article
en En
| MEDLINE
| ID: mdl-27621083
ABSTRACT
USP21 is a centrosome-associated deubiquitylase (DUB) that has been implicated in the formation of primary cilia - crucial organelles for the regulation of the Hedgehog (Hh) signaling pathway in vertebrates. Here, we identify KCTD6 - a cullin-3 E3-ligase substrate adapter that has been previously linked to Hh signaling - as well as Gli1, the key transcription factor responsible for Hh signal amplification, as new interacting partners of USP21. We identify a cryptic structured protein interaction domain in KCTD6, which is predicted to have a similar fold to Smr domains. Importantly, we show that both depletion and overexpression of catalytically active USP21 suppress Gli1-dependent transcription. Gli proteins are negatively regulated through protein kinase A (PKA)-dependent phosphorylation. We provide evidence that USP21 recruits and stabilises Gli1 at the centrosome where it promotes its phosphorylation by PKA. By revealing an intriguing functional pairing between a spatially restricted deubiquitylase and a kinase, our study highlights the centrosome as an important hub for signal coordination.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Activación Transcripcional
/
Centrosoma
/
Ubiquitina Tiolesterasa
/
Proteína con Dedos de Zinc GLI1
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Cell Sci
Año:
2016
Tipo del documento:
Article