Do septins have a role in cancer?

Russell, S. E. H.; Hall, Peter A.

doi:10.1038/sj.bjc.6602753

Cited by 75 publications

(67 citation statements)

References 32 publications

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“…The MLL fusion partner we have identified, SEPT2, belongs to an evolutionarily conserved family of genes that encode a P loop-based GTP-binding domain flanked by a polybasic domain and (usually) a coiled-coil region (Hall and Russell, 2004;Russell and Hall, 2005). The SEPT2 protein possesses all the three domains and shares a very high homology with septins 1, 4 and 5 (Hall and Russell, 2004).…”

Section: Mll-sept2 Fusion Gene In Aml N Cerveira Et Almentioning

confidence: 99%

“…The SEPT2 protein possesses all the three domains and shares a very high homology with septins 1, 4 and 5 (Hall and Russell, 2004). Recently, it has been shown that there are at least 13 human septin genes (Russell and Hall, 2005). Four of them (SEPT5, SEPT6, SEPT9 and SEPT11) have already been cloned as MLL fusion partners (Megonigal et al, 1998;Osaka et al, 1999;Taki et al, 1999a;Ono et al, 2002;Kojima et al, 2004), with the N-terminal moiety of MLL fused to almost the entire open-reading frame of the partner septin gene (Russell and Hall, 2005).…”

Section: Mll-sept2 Fusion Gene In Aml N Cerveira Et Almentioning

confidence: 99%

“…Recently, it has been shown that there are at least 13 human septin genes (Russell and Hall, 2005). Four of them (SEPT5, SEPT6, SEPT9 and SEPT11) have already been cloned as MLL fusion partners (Megonigal et al, 1998;Osaka et al, 1999;Taki et al, 1999a;Ono et al, 2002;Kojima et al, 2004), with the N-terminal moiety of MLL fused to almost the entire open-reading frame of the partner septin gene (Russell and Hall, 2005). This is the fifth septin family gene fused with the MLL gene described so far, making the septins the protein family most frequently involved in rearrangements with the MLL gene.…”

Section: Mll-sept2 Fusion Gene In Aml N Cerveira Et Almentioning

confidence: 99%

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SEPT2 is a new fusion partner of MLL in acute myeloid leukemia with t(2;11)(q37;q23)

et al. 2006

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We have identified a new mixed lineage leukemia (MLL) gene fusion partner in a patient with treatment-related acute myeloid leukemia (AML) presenting a t(2;11)(q37;q23) as the only cytogenetic abnormality. Fluorescence in situ hybridization demonstrated a rearrangement of the MLL gene and molecular genetic analyses identified a septin family gene, SEPT2, located on chromosome 2q37, as the fusion partner of MLL. RNA and DNA analyses showed the existence of an in-frame fusion of MLL exon 7 with SEPT2 exon 3, with the genomic breakpoints located in intron 7 and 2 of MLL and SEPT2, respectively. Search for DNA sequence motifs revealed the existence of two sequences with 94.4% homology with the topoisomerase II consensus cleavage site in MLL intron 7 and SEPT2 intron 2. SEPT2 is the fifth septin family gene fused with MLL, making this gene family the most frequently involved in MLL-related AML (about 10% of all known fusion partners). The protein encoded by SEPT2 is highly homologous to septins 1, 4 and 5 and is involved in the coordination of several key steps of mitosis. Further studies are warranted to understand why the septin protein family is particularly involved in the pathogenesis of MLL-associated leukemia.

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Section: Mll-sept2 Fusion Gene In Aml N Cerveira Et Almentioning

confidence: 99%

Section: Mll-sept2 Fusion Gene In Aml N Cerveira Et Almentioning

confidence: 99%

Section: Mll-sept2 Fusion Gene In Aml N Cerveira Et Almentioning

confidence: 99%

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SEPT2 is a new fusion partner of MLL in acute myeloid leukemia with t(2;11)(q37;q23)

et al. 2006

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“…Mammalian septins are evolutionary conserved proteins that form filaments associated with cytoskeleton organization, membrane dynamics, mitosis, cytokinesis, and cell cycle progression (9,10). Recently, accumulating data suggest that some septin family members also participate in the pathogenesis of neoplasia (11) and neurodegenerative diseases (12). We had shown that SEPT9_i1 interacts with HIF-1α, but not with HIF-2α, to prevent its RACK1-mediated ubiquitination and degradation (13) and that SEPT9_i1 protein activates HIF-1 transcriptional activity and increases tumor growth and angiogenesis in prostate cancer xenografts (8).…”

Section: Introductionmentioning

confidence: 99%

Targeted Knockdown of SEPT9_v1 Inhibits Tumor Growth and Angiogenesis of Human Prostate Cancer Cells Concomitant with Disruption of Hypoxia-Inducible Factor-1 Pathway

Sharon

Golan

Mabjeesh

2010

Molecular Cancer Research

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Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor in the hypoxic response pathway. We recently identified a novel interaction between HIF-1α and the mammalian septin family member, septin 9 protein, isoform 1 (SEPT9_i1), a protein product of septin 9 transcript variant 1 (SEPT9_v1). Septins are a highly conserved family of GTP-binding cytoskeletal proteins that are implicated in multiple cellular functions, including oncogenesis. SEPT9_i1 binds and stabilizes HIF-1α protein and stimulates HIF-1 transcriptional activity by preventing its RACK1-mediated ubiquitination and degradation. SEPT9_i1-HIF-1 activation promotes tumor growth and angiogenesis. The effect of SEPT9_v1 silencing in prostate cancer cells was studied. SEPT9_v1 stable knockdown was generated in PC-3 cells using a specific shRNA. SEPT9_v1 silencing reduced HIF-1α protein expression and inhibited HIF-1 transcriptional activity. SEPT9_v1 knockdown affected cell morphology, deregulated cell cycle, and decreased migration. The antiproliferative effect of shSEPT9_v1 was abolished in HIF-1α knockout colon cancer cells. In vivo, SEPT9_i1 depletion reduced HIF-1α protein expression, cellular proliferation, tumor growth, and angiogenesis. These results provide new insights and validation for applying SEPT9_v1 as a potential target for antitumor therapy by interrupting the HIF-1 pathway. Mol Cancer Res; 8(5); 643-52. ©2010 AACR.

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“…Septins are found in all eukaryotes except higher plants (20,52) and are involved in a variety of cellular processes including cytokinesis, vesicle trafficking, cytoskeleton organization, polarity, and formation of diffusion barriers (35,39,44,53,62). Perhaps, not surprisingly given their roles in such critical processes, septin defects have been associated with many human diseases (29).…”

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confidence: 99%

The Septin AspB in Aspergillus nidulans Forms Bars and Filaments and Plays Roles in Growth Emergence and Conidiation

2012

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In yeast, septins form rings at the mother-bud neck and function as diffusion barriers. In animals, septins form filaments that can colocalize with other cytoskeletal elements. In the filamentous fungus Aspergillus nidulans there are five septin genes, aspA (an ortholog of Saccharomyces cerevisiae CDC11), aspB (an ortholog of S. cerevisiae CDC3), aspC (an ortholog of S. cerevisiae CDC12), aspD (an ortholog of S. cerevisiae CDC10), and aspE (found only in filamentous fungi). The aspB gene was previously reported to be the most highly expressed Aspergillus nidulans septin and to be essential. Using improved gene targeting techniques, we found that deletion of aspB is not lethal but results in delayed septation, increased emergence of germ tubes and branches, and greatly reduced conidiation. We also found that AspB-green fluorescent protein (GFP) localizes as rings and collars at septa, branches, and emerging layers of the conidiophore and as bars and filaments in conidia and hyphae. Bars are found in dormant and isotropically expanding conidia and in subapical nongrowing regions of hyphae and display fast movements. Filaments form as the germ tube emerges, localize to hyphal and branch tips, and display slower movements. All visible AspB-GFP structures are retained in ⌬aspD and lost in ⌬aspA and ⌬aspC strains. Interestingly, in the ⌬aspE mutant, AspB-GFP rings, bars, and filaments are visible in early growth, but AspB-GFP rods and filaments disappear after septum formation. AspE orthologs are only found in filamentous fungi, suggesting that this class of septins might be required for stability of septin bars and filaments in highly polar cells. Septins are evolutionarily conserved GTP binding proteins that form complexes and are increasingly viewed as cytoskeletal elements (62). Septins are found in all eukaryotes except higher plants (20,52) and are involved in a variety of cellular processes including cytokinesis, vesicle trafficking, cytoskeleton organization, polarity, and formation of diffusion barriers (35,39,44,53,62). Perhaps, not surprisingly given their roles in such critical processes, septin defects have been associated with many human diseases (29).The septins were first discovered in the budding yeast Saccharomyces cerevisiae as temperature-sensitive cell cycle mutants defective in cytokinesis (31, 41). Early in the yeast cell cycle, septins localize as a cap at the future site of bud emergence. As the bud emerges, septins localize first as a ring at the mother/bud neck and later as an hourglass structure as the bud develops (25,26,37). At cytokinesis, the hourglass structure converts into two rings. Septins at the neck form diffusion barriers that keep the cellular machinery necessary for growth and cytokinesis properly localized (16,18,22,49,50,60). In addition, septins are part of the morphogenesis checkpoint that coordinates nuclear division with bud formation (37).In S. cerevisiae septins organize into hetero-oligomeric octamers that associate end to end to form nonpolar filaments (6). Electron ...

show abstract

Do septins have a role in cancer?

Cited by 75 publications

References 32 publications

SEPT2 is a new fusion partner of MLL in acute myeloid leukemia with t(2;11)(q37;q23)

SEPT2 is a new fusion partner of MLL in acute myeloid leukemia with t(2;11)(q37;q23)

Targeted Knockdown of SEPT9_v1 Inhibits Tumor Growth and Angiogenesis of Human Prostate Cancer Cells Concomitant with Disruption of Hypoxia-Inducible Factor-1 Pathway

The Septin AspB in Aspergillus nidulans Forms Bars and Filaments and Plays Roles in Growth Emergence and Conidiation

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