An actin filament branching surveillance system regulates cell cycle progression, cytokinesis and primary ciliogenesis
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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-37340-z |
| _version_ | 1831885776095281152 |
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| author | Muqing Cao Xiaoxiao Zou Chaoyi Li Zaisheng Lin Ni Wang Zhongju Zou Youqiong Ye Joachim Seemann Beth Levine Zaiming Tang Qing Zhong |
| author_facet | Muqing Cao Xiaoxiao Zou Chaoyi Li Zaisheng Lin Ni Wang Zhongju Zou Youqiong Ye Joachim Seemann Beth Levine Zaiming Tang Qing Zhong |
| author_sort | Muqing Cao |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T19:54:07Z |
| format | Article |
| id | doaj.art-5a4e7b718e5d4006ac84d208fd7b4f6c |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2025-03-21T23:33:27Z |
| publishDate | 2023-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-5a4e7b718e5d4006ac84d208fd7b4f6c2024-05-19T11:23:40ZengNature PortfolioNature Communications2041-17232023-03-0114111810.1038/s41467-023-37340-zAn actin filament branching surveillance system regulates cell cycle progression, cytokinesis and primary ciliogenesisMuqing Cao0Xiaoxiao Zou1Chaoyi Li2Zaisheng Lin3Ni Wang4Zhongju Zou5Youqiong Ye6Joachim Seemann7Beth Levine8Zaiming Tang9Qing Zhong10Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine (SJTU-SM)Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine (SJTU-SM)Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine (SJTU-SM)Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine (SJTU-SM)Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine (SJTU-SM)Center for Autophagy Research, Department of Internal Medicine, University of Texas Southwestern Medical CenterShanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of MedicineDepartment of Cell Biology, University of Texas Southwestern Medical CenterCenter for Autophagy Research, Department of Internal Medicine, University of Texas Southwestern Medical CenterKey Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine (SJTU-SM)Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine (SJTU-SM)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.https://doi.org/10.1038/s41467-023-37340-z |
| spellingShingle | Muqing Cao Xiaoxiao Zou Chaoyi Li Zaisheng Lin Ni Wang Zhongju Zou Youqiong Ye Joachim Seemann Beth Levine Zaiming Tang Qing Zhong An actin filament branching surveillance system regulates cell cycle progression, cytokinesis and primary ciliogenesis Nature Communications |
| title | An actin filament branching surveillance system regulates cell cycle progression, cytokinesis and primary ciliogenesis |
| title_full | An actin filament branching surveillance system regulates cell cycle progression, cytokinesis and primary ciliogenesis |
| title_fullStr | An actin filament branching surveillance system regulates cell cycle progression, cytokinesis and primary ciliogenesis |
| title_full_unstemmed | An actin filament branching surveillance system regulates cell cycle progression, cytokinesis and primary ciliogenesis |
| title_short | An actin filament branching surveillance system regulates cell cycle progression, cytokinesis and primary ciliogenesis |
| title_sort | actin filament branching surveillance system regulates cell cycle progression cytokinesis and primary ciliogenesis |
| url | https://doi.org/10.1038/s41467-023-37340-z |
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