Bora, CEP192 and Cenexin regulate distinct Plk1-dependent cell and centrosome cycle transitions

Article Article scientifique Article Bora, CEP192 and Cenexin regulate distinct Plk1-dependent cell and centrosome cycle transitions eng 2026-06-30 2026-06-30 author Dwivedi Devashish 0000-0002-2039-6570 930841 Département de physiologie cellulaire et métabolisme (PHYME) author Da Costa Horta Borges Crisálida 0009-0009-8370-0232 957752 Département de physiologie cellulaire et métabolisme (PHYME) author Harry Daniela 23513 Département de physiologie cellulaire et métabolisme (PHYME) author Cirillo Luca author Meraldi Patrick 0000-0001-9742-8756 108140 Département de physiologie cellulaire et métabolisme (PHYME) 8158 10.1038/s41467-026-75033-5 42380115 2041-1723 PMC13458439 https://www.nature.com/articles/s41467-026-75033-5 Polo-like kinase 1 (Plk1) regulates multiple steps of the cell and centrosome cycle, including mitotic entry, DNA-damage recovery, centrosome maturation and centriole disengagement. Plk1 activity depends on several independent cofactors, such as the cytoplasmic Bora, and the centrosomal proteins Cep192 and Cenexin. However, whether these Plk1 coactivators differentially regulate the Plk1-dependent processes is unknown. Here, we show that each Plk1 coactivator controls different cell and centrosome cycle transitions in human cells. We find that Plk1 already acts in S-phase, where under the control of Cep192 and Aurora A it promotes replication origin firing. Bora is the main Plk1 activator driving mitotic entry, DNA-damage recovery and centrosome maturation in G2, while centriole disengagement is mainly regulated by Cep192 and Cenexin. Our results thus uncover a complex Plk1 activation regulatory network, in which distinct upstream activators dictate its activity in a context-dependent manner. Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism Cell Cycle / physiology Centrioles / metabolism Centrosomal Associated Proteins / genetics Centrosomal Associated Proteins / metabolism Centrosome / metabolism Chromosomal Proteins, Non-Histone / genetics Chromosomal Proteins, Non-Histone / metabolism DNA Damage HeLa Cells Humans Mitosis Polo-Like Kinase 1 Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism Proto-Oncogene Proteins / genetics Proto-Oncogene Proteins / metabolism Dewey 610 Dewey 612 Swiss National Science Foundation Investigating the control and function of spindle microtubule dynamics 208052 CH Swiss National Science Foundation Polo like kinase 1 regulation and function in cell division and development 175850 CH 134 Département de physiologie cellulaire et métabolisme 21C 4f7589ed-e44d-4850-a4d8-b0c1eccdfe48 Centre de recherche translationnelle en onco-hématologie 209 false 579 Groupe Meraldi Patrick (physiologie cellulaire et métabolisme) 922 https://doi.org/10.26037/yareta:7rmgsonvwne33i42slk3uf2yfi Nature communications 17 1 15704947-9234-4122-b169-a6bb3d645642 Article (Published version) Public s41467-026-75033-5.pdf 6925123 application/pdf CC BY-4.0 5ab6734406831049113a3590525c9e42eb8fac296c0e4cd4ea01b4814e7188f9 cb3ff565-9032-4664-9508-4e12ffbc36c8 Supplemental data Public 41467_2026_75033_MOESM1_ESM.pdf 79193193 application/pdf 880d9d2ecd4cf28b9471a886850f84a8d0831a6171ac9639f29723e2a80ed6d1 83924683-9072-4666-89a3-d5b67a0c4b74 Supplemental data Public 41467_2026_75033_MOESM2_ESM.pdf 19234 application/pdf afc67dc9fd2fe50fef843fe7bcf50b12c419f916f67bee43cc4b3e6cc09170d6 24bcf292-107b-4f74-94f0-79a23d4d3c58 Supplemental data Public 41467_2026_75033_MOESM3_ESM.avi 1383584 application/x-troff-msvideo e98733cb5e45c7c9ed6ad5541c945ac16e567d0faf1ad04321efca4848e4df7f e426caee-60d0-4271-a23b-ace37893eb4d Supplemental data Public 41467_2026_75033_MOESM4_ESM.avi 717410 application/x-troff-msvideo 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543a183e7123fbba9e4946d0f46a1a9b30d5c5e029d738ed32f7f7d836718f76 openAccess Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme Faculté de médecine / Centre de recherche translationnelle en onco-hématologie

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Tipping the balance: synthesis and evaluation of centrinone-based degraders of polo-like kinase 4	RSC chemical biology	2026	8	12
Bora, CEP192 and Cenexin regulate distinct Plk1-dependent cell and centrosome cycle transitions	Nature communications	2026	4	2

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