Gorry, Rebecca L.Rebecca L.GorryBrennan, KieranKieranBrennanLavin, Paul T. M.Paul T. M.LavinMazurski, TaylerTaylerMazurskiMary, CharlineCharlineMaryMatallanas, DavidDavidMatallanasGuichou, Jean-FrançoisJean-FrançoisGuichouMc Gee, Margaret M.Margaret M.Mc Gee2025-04-012025-04-012023 the A2023-07-04International Journal of Molecular Sciences1661-6596http://hdl.handle.net/10197/27835The isomerase activity of Cyclophilin A is important for midbody abscission during cell division, however, to date, midbody substrates remain unknown. In this study, we report that the GTP-binding protein Septin 2 interacts with Cyclophilin A. We highlight a dynamic series of Septin 2 phenotypes at the midbody, previously undescribed in human cells. Furthermore, Cyclophilin A depletion or loss of isomerase activity is sufficient to induce phenotypic Septin 2 defects at the midbody. Structural and molecular analysis reveals that Septin 2 proline 259 is important for interaction with Cyclophilin A. Moreover, an isomerisation-deficient EGFP-Septin 2 proline 259 mutant displays defective midbody localisation and undergoes impaired abscission, which is consistent with data from cells with loss of Cyclophilin A expression or activity. Collectively, these data reveal Septin 2 as a novel interacting partner and isomerase substrate of Cyclophilin A at the midbody that is required for abscission during cytokinesis in cancer cells.ElectronicenHumansCyclophilin ACytokinesisSeptinsCell divisionHela cellsJournal Article241310.3390/ijms2413110842025-02-1911/RFP.1/CAN/320215/CDA/3495204844/Z/16/Z15/CDA/3495https://creativecommons.org/licenses/by/3.0/ie/