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ABSTRACT: Snail family proteins regulate transcription of molecules for cell-cell adhesion during epithelial-mesenchymal transition (EMT). Based on putative glycogen synthase kinase 3β (GSK-3β) phosphorylation sites within the Slug/Snail2, we explored the significance of GSK-3β-mediated phosphorylation in Slug/Snail2 expression during EMT. Mutation of the putative GSK-3β phosphorylation sites (S92/96A or S100/104A) enhanced the Slug/Snail2-mediated EMT properties of E-cadherin repression and vimentin induction, compared with wild-type Slug/Snail2. S92/96A mutation inhibited degradation of Slug/Snail2 and S100/104A mutation extended nuclear stabilization. Inhibition of GSK-3β activity caused similar effects, as did the phosphorylation mutations. Thus, our study suggests that GSK-3β-mediated phosphorylation of Slug/Snail2 controls its turnover and localization during EMT.
FEBS Journal 06/2012; 279(16):2929-39. · 3.79 Impact Factor
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ABSTRACT: Transmembrane 4 L six family member 5 (TM4SF5) is highly expressed in hepatocarcinoma and causes epithelial-mesenchymal transition (EMT) of hepatocytes. We found that TM4SF5-expressing cells showed lower mRNA levels but maintained normal protein levels in certain gene cases, indicating that TM4SF5 mediates stabilization of proteins. In this study, we explored whether regulation of proteasome activity and TM4SF5 expression led to EMT. We observed that TM4SF5 expression caused inhibition of proteasome activity and proteasome subunit expression, causing morphological changes and loss of cell-cell contacts. shRNA against TM4SF5 recovered proteasome expression, with leading to blockade of proteasome inactivation and EMT. Altogether, TM4SF5 expression appeared to cause loss of cell-cell adhesions via proteasome suppression and thereby proteasome inhibition, leading to repression of cell-cell adhesion molecules, such as E-cadherin.
Journal of Cellular Biochemistry 03/2011; 112(3):782-92. · 2.87 Impact Factor
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ABSTRACT: Transmembrane 4 L six family member 5 (TM4SF5) is highly expressed in hepatocarcinoma and causes epithelial–mesenchymal transition (EMT) of hepatocytes. We found that TM4SF5-expressing cells showed lower mRNA levels but maintained normal protein levels in certain gene cases, indicating that TM4SF5 mediates stabilization of proteins. In this study, we explored whether regulation of proteasome activity and TM4SF5 expression led to EMT. We observed that TM4SF5 expression caused inhibition of proteasome activity and proteasome subunit expression, causing morphological changes and loss of cell–cell contacts. shRNA against TM4SF5 recovered proteasome expression, with leading to blockade of proteasome inactivation and EMT. Altogether, TM4SF5 expression appeared to cause loss of cell–cell adhesions via proteasome suppression and thereby proteasome inhibition, leading to repression of cell–cell adhesion molecules, such as E-cadherin. J. Cell. Biochem. 112: 782–792, 2011. © 2010 Wiley-Liss, Inc.
Journal of Cellular Biochemistry 02/2011; 112(3):782 - 792. · 2.87 Impact Factor
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ABSTRACT: Chronic granulomatous disease (CGD) is a rare hereditary disorder characterized by recurrent life-threatening bacterial and fungal infections. The underlying defect in CGD is an inability of phagocytes to produce reactive oxygen species as a result of defects in NADPH oxidase. Considering that CGD generally affects about 3-4 in 1,000,000 individuals, it is surprising that the prevalence of CGD on Jeju Island is 20.7 in 1,000,000 individuals. We performed genetic analysis on 12 patients from 10 unrelated families and found that all patients had an identical homozygous single-base substitution of C to T in exon 1 (c.7C>T) of the CYBA gene, which was expected to result in a nonsense mutation (p.Q3X). Because Jeju Island has long been a geologically isolated region, the high prevalence of CGD on Jeju Island is presumably associated with an identical mutation inherited from a common ancestor or proband.
Journal of Korean medical science 12/2009; 24(6):1045-50. · 0.84 Impact Factor
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ABSTRACT: The galectin family of lectins plays crucial roles in the innate immunity systems of vertebrates and invertebrates. Noble galectin (MCGal) was cloned from the marine invertebrate Ruditapes philippinarum and characterized. This protein has an open reading frame of 918 nucleotides, with 309 amino acid residues, and a predicted molecular weight of 33.9kDa. Similar to other galectins, MCGal has neither a signal peptide nor a transmembrane domain, but it contains tandemly repeated carbohydrate recognition domains (CRDs), with typical conserved motifs that are important for carbohydrate recognition. Carbohydrate recognition by the recombinant MCGal (rMCGal), as determined by hapten inhibition of hemagglutination, revealed that rMCGal has features common to the galectin family, i.e., significant affinity for galactose and N-acetylgalactosamine. MCGal mRNA expression was detected mainly in the heart, mantle, foot, adductor, palp, and siphon tissues. Immunohistochemistry (IHC) using an anti-MCGal antibody confirmed MCGal expression in these tissues and in hemocytes. Temporal expression of MCGal mRNA in Manila clams challenged with Perkinsus or Vibrio species was up-regulated as compared with non-challenged healthy clams. rMCGal agglutinated Vibrio tapetis, and agglutination was inhibited by incubation with alpha-lactose. rMCGal also bound to the surface of Perkinsus olseni. MCGal plays a crucial role in Manila clam defense, particularly with respect to pathogen recognition.
Developmental & Comparative Immunology 02/2008; 32(10):1131-41. · 3.27 Impact Factor
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ABSTRACT: A novel C-type lectin designated Manila clam lectin 3 (MCL3), with a molecular weight of 17.380 kDa, was identified among haemocyte expressed sequence tags of Perkinsus olseni-infected Manila clams. MCL3 was expressed in Escherichia coli M15 cells and purified with a Ni-NTA His-binding resin matrix. MCL3 agglutinated rabbit erythrocytes in the presence of Ca+2. MCL3-induced agglutination was partially inhibited by GalNAc, Man, lactose, and raffinose, whereas the polysaccharides bovine mucin type II and Candida mannan completely inhibited agglutination. MCL3 was expressed in the haemocytes of Manila clams 3 days after infection with P. olseni and 1 day after infection with Vibrio tapetis. Based on real-time PCR analysis, mRNA transcripts of MCL3 were present in the adductor, foot, gill, mantle, palp, and siphon of Perkinsus-infected Manila clams. Furthermore, MCL3 was detected in the foot, gill, mantle, gonad, digestive gland, gonad connective tissue, intestine, and stomach by immunohistochemical localization.
Fish & Shellfish Immunology.
