Two NEMO-like Ubiquitin-Binding Domains in CEP55 Differently Regulate Cytokinesis
Summary: CEP55 regulates the final critical step of cell division termed cytokinetic abscission. We report herein that CEP55 contains two NEMO-like ubiquitin-binding domains (UBDs), NOA and ZF, which regulate its function in a different manner. In vitro studies of isolated domains showed that NOA ad...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-10-01
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| Series: | iScience |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004219303207 |
| _version_ | 1818836400593698816 |
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| author | Keïs Nabhane Said Halidi Elisabeth Fontan Alix Boucharlat Laurianne Davignon Marine Charpentier Mikaël Boullé Robert Weil Alain Israël Emmanuel Laplantine Fabrice Agou |
| author_facet | Keïs Nabhane Said Halidi Elisabeth Fontan Alix Boucharlat Laurianne Davignon Marine Charpentier Mikaël Boullé Robert Weil Alain Israël Emmanuel Laplantine Fabrice Agou |
| author_sort | Keïs Nabhane Said Halidi |
| collection | DOAJ |
| description | Summary: CEP55 regulates the final critical step of cell division termed cytokinetic abscission. We report herein that CEP55 contains two NEMO-like ubiquitin-binding domains (UBDs), NOA and ZF, which regulate its function in a different manner. In vitro studies of isolated domains showed that NOA adopts a dimeric coiled-coil structure, whereas ZF is based on a UBZ scaffold. Strikingly, CEP55 knocked-down HeLa cells reconstituted with the full-length CEP55 ubiquitin-binding defective mutants, containing structure-guided mutations either in NOACEP55 or ZFCEP55 domains, display severe abscission defects. In addition, the ZFCEP55 can be functionally replaced by some ZF-based UBDs belonging to the UBZ family, indicating that the essential function of ZFCEP55 is to act as ubiquitin receptor. Our work reveals an unexpected role of CEP55 in non-degradative ubiquitin signaling during cytokinetic abscission and provides a molecular basis as to how CEP55 mutations can lead to neurological disorders such as the MARCH syndrome. : Biochemistry; Cell Biology; Structural Biology; Protein Structure Aspects Subject Areas: Biochemistry, Cell Biology, Structural Biology, Protein Structure Aspects |
| first_indexed | 2024-12-19T03:06:00Z |
| format | Article |
| id | doaj.art-43528c8ba79d41b8a1bd87154ceacfe4 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-19T03:06:00Z |
| publishDate | 2019-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-43528c8ba79d41b8a1bd87154ceacfe42022-12-21T20:38:06ZengElsevieriScience2589-00422019-10-0120292309Two NEMO-like Ubiquitin-Binding Domains in CEP55 Differently Regulate CytokinesisKeïs Nabhane Said Halidi0Elisabeth Fontan1Alix Boucharlat2Laurianne Davignon3Marine Charpentier4Mikaël Boullé5Robert Weil6Alain Israël7Emmanuel Laplantine8Fabrice Agou9Chemogenomic and Biological Screening Core Facility, C2RT, Departments of Cell Biology & Infection and of Structural Biology and Chemistry, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris CEDEX 15, France; Sorbonne Université, Collège doctoral, 75005 Paris, FranceChemogenomic and Biological Screening Core Facility, C2RT, Departments of Cell Biology & Infection and of Structural Biology and Chemistry, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris CEDEX 15, FranceChemogenomic and Biological Screening Core Facility, C2RT, Departments of Cell Biology & Infection and of Structural Biology and Chemistry, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris CEDEX 15, FranceChemogenomic and Biological Screening Core Facility, C2RT, Departments of Cell Biology & Infection and of Structural Biology and Chemistry, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris CEDEX 15, FranceChemogenomic and Biological Screening Core Facility, C2RT, Departments of Cell Biology & Infection and of Structural Biology and Chemistry, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris CEDEX 15, FranceChemogenomic and Biological Screening Core Facility, C2RT, Departments of Cell Biology & Infection and of Structural Biology and Chemistry, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris CEDEX 15, France; Université de Paris, Sorbonne Paris Cité, Paris, FranceSignaling and Pathogenesis Laboratory, Department of Cell Biology & Infection, Institut Pasteur, C.N.R.S UMR 3691, 25 rue du Dr. Roux, 75724 Paris CEDEX 15, FranceDepartment of Cell Biology & Infection, Institut Pasteur, 75724 Paris CEDEX 15, FranceSignaling and Pathogenesis Laboratory, Department of Cell Biology & Infection, Institut Pasteur, C.N.R.S UMR 3691, 25 rue du Dr. Roux, 75724 Paris CEDEX 15, France; Corresponding authorChemogenomic and Biological Screening Core Facility, C2RT, Departments of Cell Biology & Infection and of Structural Biology and Chemistry, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris CEDEX 15, France; Corresponding authorSummary: CEP55 regulates the final critical step of cell division termed cytokinetic abscission. We report herein that CEP55 contains two NEMO-like ubiquitin-binding domains (UBDs), NOA and ZF, which regulate its function in a different manner. In vitro studies of isolated domains showed that NOA adopts a dimeric coiled-coil structure, whereas ZF is based on a UBZ scaffold. Strikingly, CEP55 knocked-down HeLa cells reconstituted with the full-length CEP55 ubiquitin-binding defective mutants, containing structure-guided mutations either in NOACEP55 or ZFCEP55 domains, display severe abscission defects. In addition, the ZFCEP55 can be functionally replaced by some ZF-based UBDs belonging to the UBZ family, indicating that the essential function of ZFCEP55 is to act as ubiquitin receptor. Our work reveals an unexpected role of CEP55 in non-degradative ubiquitin signaling during cytokinetic abscission and provides a molecular basis as to how CEP55 mutations can lead to neurological disorders such as the MARCH syndrome. : Biochemistry; Cell Biology; Structural Biology; Protein Structure Aspects Subject Areas: Biochemistry, Cell Biology, Structural Biology, Protein Structure Aspectshttp://www.sciencedirect.com/science/article/pii/S2589004219303207 |
| spellingShingle | Keïs Nabhane Said Halidi Elisabeth Fontan Alix Boucharlat Laurianne Davignon Marine Charpentier Mikaël Boullé Robert Weil Alain Israël Emmanuel Laplantine Fabrice Agou Two NEMO-like Ubiquitin-Binding Domains in CEP55 Differently Regulate Cytokinesis iScience |
| title | Two NEMO-like Ubiquitin-Binding Domains in CEP55 Differently Regulate Cytokinesis |
| title_full | Two NEMO-like Ubiquitin-Binding Domains in CEP55 Differently Regulate Cytokinesis |
| title_fullStr | Two NEMO-like Ubiquitin-Binding Domains in CEP55 Differently Regulate Cytokinesis |
| title_full_unstemmed | Two NEMO-like Ubiquitin-Binding Domains in CEP55 Differently Regulate Cytokinesis |
| title_short | Two NEMO-like Ubiquitin-Binding Domains in CEP55 Differently Regulate Cytokinesis |
| title_sort | two nemo like ubiquitin binding domains in cep55 differently regulate cytokinesis |
| url | http://www.sciencedirect.com/science/article/pii/S2589004219303207 |
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