An actin filament branching surveillance system regulates cell cycle progression, cytokinesis and primary ciliogenesis

Muqing Cao (), Xiaoxiao Zou, Chaoyi Li, Zaisheng Lin, Ni Wang, Zhongju Zou, Youqiong Ye, Joachim Seemann, Beth Levine, Zaiming Tang () and Qing Zhong ()
Additional contact information
Muqing Cao: Shanghai Jiao Tong University School of Medicine (SJTU-SM)
Xiaoxiao Zou: Shanghai Jiao Tong University School of Medicine (SJTU-SM)
Chaoyi Li: Shanghai Jiao Tong University School of Medicine (SJTU-SM)
Zaisheng Lin: Shanghai Jiao Tong University School of Medicine (SJTU-SM)
Ni Wang: Shanghai Jiao Tong University School of Medicine (SJTU-SM)
Zhongju Zou: University of Texas Southwestern Medical Center
Youqiong Ye: Shanghai Jiao Tong University School of Medicine
Joachim Seemann: University of Texas Southwestern Medical Center
Beth Levine: University of Texas Southwestern Medical Center
Zaiming Tang: Shanghai Jiao Tong University School of Medicine (SJTU-SM)
Qing Zhong: Shanghai Jiao Tong University School of Medicine (SJTU-SM)

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: 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.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-37340-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37340-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-37340-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().