Highlight: The 5th International Workshop on Septin Biology

Mostowy, Serge; Bi, Erfei; Füchtbauer, Ernst Martin; Goryachev, Andrew B.; Montagna, Cristina; Nagata, Koh Ichi; Trimble, William S.; Werner, Hauke; Yao, Xuebiao; Zieger, Barbara; Spiliotis, Elias T.

doi:10.1515/hsz-2013-0291

Cited by 3 publications

(2 citation statements)

References 22 publications

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“…According to sequence similarity, all isoforms have been classified into the four subgroups: Sept2, Sept3, Sept6 and Sept7 (Kinoshita, 2003a). Nowadays, septins have been identified in many other eukaryotes, ranging from fungi to humans (Kinoshita, 2003b;Sandrock et al, 2011;Mostowy et al, 2014), except for plants (Oh and Bi, 2011). When purified from cells and tissues, septins assembled into the Sept2-Sept6-Sept7 apolar hexamer complex (Sellin et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Methylation of Septin9 mediated by DNMT3a enhances hepatic stellate cells activation and liver fibrogenesis

Hou

et al. 2017

Toxicology and Applied Pharmacology

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Liver fibrosis, resulting from chronic and persistent injury to the liver, is a worldwide health problem. Advanced liver fibrosis results in cirrhosis, liver failure and even hepatocellular cancer (HCC), often eventually requiring liver transplantation, poses a huge health burden on the global community. However, the specific pathogenesis of liver fibrosis remains not fully understood. Numerous basic and clinical studies have provided evidence that epigenetic modifications, especially DNA methylation, might contribute to the activation of hepatic stellate cells (HSCs), the pivotal cell type responsible for the fibrous scar in liver. Here, reduced representation bisulfite sequencing (RRBS) and bisulfite pyrosequencing PCR (BSP) analysis identified hypermethylation status of Septin9 (Sept9) gene in liver fibrogenesis. Sept9 protein was dramatically decreased in livers of CCl4-treated mice and immortalized HSC-T6 cells exposed to TGF-β1. Nevertheless, the suppression of Sept9 could be blocked by DNMT3a-siRNA and DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (5-azadC). Overexpressed Sept9 attenuated TGF-β1-induced expression of myofibroblast markers α-SMA and Col1a1, accompanied by up-regulation of cell apoptosis-related proteins. Conversely, RNAi-mediated silencing of Sept9 enhanced accumulation of extracellular matrix. These observations suggested that Sept9 contributed to alleviate liver fibrosis might partially through promoting activated HSCs apoptosis and this anti-fibrogenesis effect might be blocked by DNMT-3a mediated methylation of Sept9. Therefore, pharmacological agents that inhibit Sept9 methylation and increase its expression could be considered as valuable treatments for liver fibrosis.

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Section: Discussionmentioning

confidence: 99%

Methylation of Septin9 mediated by DNMT3a enhances hepatic stellate cells activation and liver fibrogenesis

Hou

et al. 2017

Toxicology and Applied Pharmacology

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“…Human septin misregulation is associated with numerous disease states, which range from cancers to neurodegenerative disorders (13). For example, septin expression levels are altered in a variety of solid tumors, and recently, it has been shown that cell lines overexpressing individual septins are better at crawling in two-dimensional and three-dimensional matrices (14,15). In addition, the methylation status of septin 9 DNA is gaining use as a blood screening tool for colorectal cancers (16,17).…”

mentioning

confidence: 99%

Septin Form and Function at the Cell Cortex

Bridges

Gladfelter

2015

Journal of Biological Chemistry

129

138

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Septins are a conserved family of cytoskeletal GTP-binding proteins that function in cytokinesis, cell polarity, and membrane remodeling in many eukaryotic cell types (1, 2). To contribute to these diverse process, septins polymerize into filaments and higher-order structures that organize the cell cortex into domains that are tightly controlled in time and/or space (3). Higher-order septin structures act to recruit and/or integrate protein networks at specific locations, an example being contractile ring components in cell division (4 -7). In addition, septins are thought to alter lateral diffusion of proteins embedded in the plasma and endoplasmic reticulum (ER) 2 membranes and may influence local lipid composition (8 -10). In addition to membrane association, septins interact with, respond to, and organize the actin and microtubule cytoskeletons (11). Although septins were discovered by Hartwell, Pringle, and colleagues (12) in cell division cycle screens decades ago, understanding of septins has lagged behind other cytoskeletal systems. Recent biochemical, structural, and biophysical approaches, however, have made septins highly tractable and brought about exciting advances. Despite this recent progress, many fundamental questions remain in the septin field, in particular, the mechanisms by which septins associate with and influence the cell cortex.

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High SEPT9_i1 Protein Expression Is Associated with High-Grade Prostate Cancers

Gilad

Meir²,

Stein³

et al. 2015

PLoS ONE

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Septins are a family of GTP-binding cytoskeleton proteins expressed in many solid tumors. Septin 9 (SEPT9) in particular was found overexpressed in diverse carcinomas. Herein, we studied the expression of SEPT9 isoform 1 protein (SEPT9_i1) in human prostate cancer specimens. We utilized immunohistochemical staining to study the expression of SEPT9_i1 protein. Staining level was analyzed in association with clinical characteristics and the pathological Gleason grade and score. Fifty human prostate cancer specimens (42 primary tumors and 8 metastatic lesions) were stained by SEPT9_i1 antibody and analyzed. SEPT9_i1 protein was expressed in prostate cancer cells but absent in normal epithelial cells. The intensity of staining was correlated proportionally to pretreatment prostate-specific antigen (PSA) blood levels and Gleason score (P < 0.05). SEPT9_i1 was highly expressed in all metastatic lesions. A significant assocation between SEPT9_i1 expression and high Gleason score on multivariate linear regression analysis was found. We conclude that SEPT9_i1 is expressed in high-grade prostate tumors suggesting it has a significant role in prostate tumorigenesis and that it could serve as a molecular marker for prostate tumor progression.

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Highlight: The 5th International Workshop on Septin Biology

Cited by 3 publications

References 22 publications

Methylation of Septin9 mediated by DNMT3a enhances hepatic stellate cells activation and liver fibrogenesis

Methylation of Septin9 mediated by DNMT3a enhances hepatic stellate cells activation and liver fibrogenesis

Septin Form and Function at the Cell Cortex

High SEPT9_i1 Protein Expression Is Associated with High-Grade Prostate Cancers

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