| 2007 |
SEPTIN6 was identified as a binding partner of HCV NS5b RNA-dependent RNA polymerase by yeast two-hybrid screening, and SEPTIN6 also interacts with hnRNP A1. Knockdown of SEPTIN6 or overexpression of N-terminally truncated SEPTIN6 inhibited HCV replication, establishing a functional role for SEPTIN6 in HCV RNA replication through protein-protein interactions. |
Yeast two-hybrid screening, coimmunoprecipitation, siRNA knockdown, dominant-negative overexpression |
Journal of virology |
Medium |
17229681
|
| 2002 |
SEPTIN6 is fused to MLL in infant acute myeloid leukemia via t(X;11)(q24;q23) and related complex rearrangements, generating an MLL-SEPTIN6 fusion protein containing almost the entire SEPTIN6 sequence. SEPTIN6 encodes at least two protein isoforms by alternative splicing. The fusion protein structure parallels other MLL-septin fusions (MLL-CDCREL1, MLL-MSF), suggesting a common leukemogenic pathway. |
RT-PCR, sequencing, Southern blot, cytogenetics, FISH |
Cancer research |
Medium |
11477664 11809673 12096348 18492691
|
| 2002 |
The MLL genomic breakpoint in the MLL-SEPTIN6 rearrangement was identified as a functional DNA topoisomerase II cleavage site in an in vitro cleavage assay, implicating topoisomerase II activity in generating the chromosomal translocation. |
In vitro topoisomerase II cleavage assay, panhandle PCR, Southern blot |
Oncogene |
Medium |
12096348
|
| 2005 |
Sept6-deficient mice showed no gross abnormalities, no cytokinesis defects, and no spontaneous malignancy. Loss of Sept6 did not alter levels of other septins, did not worsen the Sept4-null phenotype, and did not affect the myeloproliferative disease induced by MLL-SEPT6, indicating that SEPT6 does not function as a tumor suppressor and that there is high redundancy within the septin system. |
Gene knockout (Sept6-deficient mice), bone marrow transplantation, retroviral MLL-SEPT6 expression, in vitro siRNA of Sept11 |
Molecular and cellular biology |
High |
16314519
|
| 2011 |
SEPT6 localizes to branch points of developing dendrites and to bases of filopodia and spines in hippocampal neurons, forming ring-like structures (~0.5 μm diameter). SEPT6 is expressed beginning at stage 4 (dendritic outgrowth) and is not a post-synaptic density (PSD) protein. RNAi knockdown of SEPT6 at early developmental stage significantly reduced dendritic length and branch number, demonstrating a role in dendritic cytoarchitecture. |
Immunocytochemistry, detergent extraction fractionation, RNAi knockdown with morphological quantification in dissociated hippocampal cultures |
Molecules and cells |
Medium |
21544625
|
| 2014 |
SEPT6 and SEPT7 complexes bound to F-actin regulate protein sorting during multivesicular body (MVB) biogenesis. These complexes bind the AP-3 adaptor complex, modulate AP-3 membrane interactions and motility of AP-3-positive endosomes. SEPT6/SEPT7 interactions also influence membrane association of ESCRT-I, coordinating two cargo-sorting machineries during MVB biogenesis. This coordination requires the E3 ubiquitin ligase LRSAM1. |
Co-immunoprecipitation, siRNA knockdown, live-cell imaging of endosome motility, subcellular fractionation |
PloS one |
Medium |
25380047
|
| 2007 |
SEPT12 interacts with SEPT6 both in vitro and in vivo (in HeLa cells), independently of the SEPT6 coiled-coil domain. Co-expression of SEPT12 altered the filamentous structure of SEPT6 in HeLa cells, demonstrating that septin-septin interactions modulate SEPT6 filament organization. |
Co-immunoprecipitation, in vitro binding assay, co-expression with fluorescence microscopy in HeLa cells, deletion mutant analysis |
Journal of biochemistry and molecular biology |
Medium |
18047794
|
| 2021 |
LSD1 demethylates the SEPT6 promoter to positively regulate SEPT6 expression at the transcriptional level. LSD1-mediated upregulation of SEPT6 activates the TGF-β1/Smad signaling pathway to promote NSCLC cell proliferation, migration, invasion, and in vivo metastasis. |
Lentivirus-mediated LSD1 silencing and SEPT6 overexpression, RT-qPCR, western blotting, EdU proliferation assay, Transwell assay, flow cytometry, xenograft mouse model |
Cancer gene therapy |
Medium |
33664458
|
| 2021 |
SEPT6 promotes HCC cell proliferation, migration, and invasion by facilitating F-actin formation, which leads to LATS1 dephosphorylation, Hippo pathway inhibition, and YAP nuclear translocation with downstream upregulation of cyclin D1 and MMP2. YAP overexpression rescued SEPT6-knockdown phenotypes and YAP knockdown blocked SEPT6-overexpression effects, placing SEPT6 upstream of YAP in HCC. |
Stable knockdown/overexpression cell lines, CCK-8, flow cytometry, Transwell assay, YAP rescue and knockdown epistasis, western blotting |
International journal of oncology |
Medium |
33846777
|
| 2018 |
SEPT6 overexpression in hepatic stellate cells (HSCs) promotes TGF-β1 expression and phosphorylation of Smad2, Smad3, ERK, JNK, SAPK-2, and AKT, driving fibrogenic activation. Blockade of TGF-β1/Smad signaling reversed SEPT6 overexpression effects on α-SMA, cyclin D1, BCL2, and MMP-2/-9. In vivo, adenovirus-mediated SEPT6 inhibition attenuated TAA-induced liver fibrosis in rats. |
Overexpression/knockdown in HSC lines, pharmacological TGF-β1/Smad blockade (SB431542), in vivo adenovirus-mediated knockdown in rat fibrosis model, western blotting |
Laboratory investigation |
Medium |
30315255
|
| 2017 |
SEPT6-deficient hematopoietic stem cells (HSCs) exhibit increased engraftment potential but impaired lymphoid differentiation, with reduced T-cell and increased B-cell contribution. Multipotent progenitor cells showed distinct SEPT6 filament organization but were functionally unimpaired by SEPT6 deficiency, indicating SEPT6 specifically regulates long-term HSC function and lymphoid lineage choice. |
Sept6-deficient mouse model, bone marrow transplantation, flow cytometry of hematopoietic lineages, fluorescence microscopy of septin filaments |
Experimental hematology |
Medium |
28751190
|
| 2021 |
A germline stop-loss mutation in SEPT6 caused X-linked congenital neutropenia with myeloid tetraploidy in a male infant. Reduced SEPT6 staining was found in bone marrow granulocyte precursors and megakaryocytes. SEPT6 KO in an erythroid cell line produced multinucleation. In silico modeling predicted the mutation disrupts SEPT6 coiled-coil dimerization, impairing filament formation. These data establish a critical role for SEPT6 in chromosomal segregation in myeloid progenitors. |
Next-generation sequencing, CRISPR/Cas9 knock-in and knockout, iPSC myeloid colony assay, immunohistochemistry, in silico structural modeling |
American journal of hematology |
Medium |
34677878
|
| 2023 |
Zebrafish Sept6-null mutants are viable without gross developmental defects but are more susceptible to Shigella infection, demonstrating a role for Sept6 in host defence against intracellular bacterial pathogens in vivo. |
CRISPR/Cas9 null mutant generation, in vivo Shigella infection model in zebrafish larvae, survival analysis, RT-qPCR of other septin genes |
Cytoskeleton (Hoboken, N.J.) |
Medium |
36855298
|
| 2018 |
In stored platelets, miR-223 directly targets the 3'UTR of SEPT6 mRNA and downregulates SEPT6 expression. SEPT6 mRNA co-immunoprecipitates with AGO2 in platelet extracts, and a luciferase reporter with SEPT6 3'UTR is downregulated by miR-223, establishing miR-223 as a post-transcriptional regulator of SEPT6 in platelets. |
AGO2 co-immunoprecipitation, luciferase reporter assay with SEPT6 3'UTR, anti-miR-223 rescue in platelets |
MicroRNA (Shariqah, United Arab Emirates) |
Medium |
29943706
|
| 2025 |
SEPT6 undergoes liquid-liquid phase separation (LLPS) both in vitro and in vivo in polarized epithelial (MDCK) cells, mediated by weak, multivalent interactions through its C-terminal tail. SEPT6 mutants defective in LLPS in vitro also fail to support adherens junction integrity and cell polarity establishment in 2D and 3D cultures, demonstrating that LLPS-competent SEPT6 is required for epithelial polarity. |
In vitro LLPS assay, live-cell imaging of septin dynamics in MDCK cells, SEPT6 C-terminal tail mutant analysis, 3D lumen formation assay |
Journal of molecular cell biology |
Medium |
39973116
|
| 2021 |
SEPT6 acts upstream of UBC (ubiquitin C) in prostate cancer cells: SEPT6 overexpression decreased UBC expression while SEPT6 knockdown increased it, and SEPT6 co-localizes with UBC in prostate cancer cells by immunofluorescence. SEPT6 inhibited tumor growth in vivo through this UBC-mediated reduction of overall ubiquitination levels. |
Overexpression/knockdown, immunofluorescence co-localization, CCK-8, flow cytometry, xenograft tumor formation |
Mediators of inflammation |
Low |
34966246
|
| 2019 |
SEPT6 overexpression in dairy cow mammary epithelial cells upregulates mTOR, p-mTOR, S6K1, and p-S6K1, promoting cell growth and casein (CSN2) synthesis. mTOR inhibition blocked the effects of SEPT6 overexpression, placing SEPT6 upstream of the mTORC1 pathway in amino acid-mediated casein synthesis. |
Overexpression/inhibition of SEPT6, mTOR inhibition rescue, western blotting, cell growth assays in primary dairy cow mammary epithelial cells |
The Journal of dairy research |
Low |
31122298
|