biostudies-literatureDevlin LPennsylvania Department of HealthNational Institute of General Medical SciencesNIGMS NIH HHSe2100155https://www.ebi.ac.uk/biostudies/studies/S-EPMC8612247biostudies-literatureUnknown21(19)Septins are a family of multimeric GTP-binding proteins, which are abnormally expressed in cancer. Septin 9 (SEPT9) is an essential and ubiquitously expressed septin with multiple isoforms, which have differential expression patterns and effects in breast cancer cells. It is unknown, however, if SEPT9 isoforms associate with different molecular networks and functions. Here, we performed a proteomic screen in MCF-7 breast cancer cells to identify the interactome of GFP-SEPT9 isoforms 1, 4 and 5, which vary significantly in their N-terminal extensions. While all three isoforms associated with SEPT2 and SEPT7, the truncated SEPT9_i4 and SEPT9_i5 interacted with septins of the SEPT6 group more promiscuously than SEPT9_i1, which bound predominately SEPT8. Spatial mapping and functional clusteriProteomicsProteomic profiling of the oncogenic septin 9 reveals isoform-specific interactions in breast cancer cells.PMC8612247R35 GM136337R01 GM097664SAP 4100079710Nakos KOkletey JSpiliotis ETPerkins GBowen JRMontagna CDevlin LfalseProteomic profiling of the oncogenic septin 9 reveals isoform-specific interactions in breast cancer cells.Septins are a family of multimeric GTP-binding proteins, which are abnormally expressed in cancer. Septin 9 (SEPT9) is an essential and ubiquitously expressed septin with multiple isoforms, which have differential expression patterns and effects in breast cancer cells. It is unknown, however, if SEPT9 isoforms associate with different molecular networks and functions. Here, we performed a proteomic screen in MCF-7 breast cancer cells to identify the interactome of GFP-SEPT9 isoforms 1, 4 and 5, which vary significantly in their N-terminal extensions. While all three isoforms associated with SEPT2 and SEPT7, the truncated SEPT9_i4 and SEPT9_i5 interacted with septins of the SEPT6 group more promiscuously than SEPT9_i1, which bound predominately SEPT8. Spatial mapping and functional clusteri2021-01-01T00:00:00Z2021 Oct2026-05-31T02:12:43.792Z2025-02-19T01:21:54.607ZS-EPMC86122473440973110.1002/pmic.202100155