Cortical tension promotes Kibra degradation via Par-1.
Journal
Molecular biology of the cell
ISSN: 1939-4586
Titre abrégé: Mol Biol Cell
Pays: United States
ID NLM: 9201390
Informations de publication
Date de publication:
01 Jan 2024
01 Jan 2024
Historique:
pubmed:
30
10
2023
medline:
30
10
2023
entrez:
30
10
2023
Statut:
ppublish
Résumé
The Hippo pathway is an evolutionarily conserved regulator of tissue growth. Multiple Hippo signaling components are regulated via proteolytic degradation. However, how these degradation mechanisms are themselves modulated remains unexplored. Kibra is a key upstream pathway activator that promotes its own ubiquitin-mediated degradation upon assembling a Hippo signaling complex. Here, we demonstrate that Hippo complex-dependent Kibra degradation is modulated by cortical tension. Using classical genetic, osmotic, and pharmacological manipulations of myosin activity and cortical tension, we show that increasing cortical tension leads to Kibra degradation, whereas decreasing cortical tension increases Kibra abundance. Our study also implicates Par-1 in regulating Kib abundance downstream of cortical tension. We demonstrate that Par-1 promotes ubiquitin-mediated Kib degradation in a Hippo complex-dependent manner and is required for tension-induced Kib degradation. Collectively, our results reveal a previously unknown molecular mechanism by which cortical tension affects Hippo signaling and provide novel insights into the role of mechanical forces in growth control.
Identifiants
pubmed: 37903240
doi: 10.1091/mbc.E23-06-0246
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM