An actin filament branching surveillance system regulates cell cycle progression, cytokinesis and primary ciliogenesis.
Nat Commun
; 14(1): 1687, 2023 03 27.
Article
em En
| MEDLINE
| ID: mdl-36973243
ABSTRACT
Dysfunction of cell cycle control and defects of primary ciliogenesis are two features of many cancers. Whether these events are interconnected and the driving mechanism coordinating them remains elusive. Here, we identify an actin filament branching surveillance system that alerts cells of actin branching insufficiency and regulates cell cycle progression, cytokinesis and primary ciliogenesis. We find that Oral-Facial-Digital syndrome 1 functions as a class II Nucleation promoting factor to promote Arp2/3 complex-mediated actin branching. Perturbation of actin branching promotes OFD1 degradation and inactivation via liquid-to-gel transition. Elimination of OFD1 or disruption of OFD1-Arp2/3 interaction drives proliferating, non-transformed cells into quiescence with ciliogenesis by an RB-dependent mechanism, while it leads oncogene-transformed/cancer cells to incomplete cytokinesis and irreversible mitotic catastrophe via actomyosin ring malformation. Inhibition of OFD1 leads to suppression of multiple cancer cell growth in mouse xenograft models. Thus, targeting OFD1-mediated actin filament branching surveillance system provides a direction for cancer therapy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Actinas
/
Citocinese
Tipo de estudo:
Prognostic_studies
/
Screening_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Commun
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China