• BMB Reports
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• v.51 no.7
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• pp.356-361
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• 2018

Actin-binding LIM protein 1 (ABLIM1), a member of the LIM-domain protein family, mediates interactions between actin filaments and cytoplasmic targets. However, the role of ABLIM1 in osteoclast and bone metabolism has not been reported. In the present study, we investigated the role of ABLIM1 in the receptor activator of $NF-{\kappa}B$ ligand (RANKL)-mediated osteoclastogenesis. ABLIM1 expression was induced by RANKL treatment and knockdown of ABLIM1 by retrovirus infection containing Ablim1-specific short hairpin RNA (shAblim1) decreased mature osteoclast formation and bone resorption activity in a RANKL-dose dependent manner. Coincident with the downregulated expression of osteoclast differentiation marker genes, the expression levels of c-Fos and the nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), critical transcription factors of osteoclastogenesis, were also decreased in shAblim1-infected osteoclasts during RANKL-mediated osteoclast differentiation. In addition, the motility of preosteoclast was reduced by ABLIM1 knockdown via modulation of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt/Rac1 signaling pathway, suggesting another regulatory mechanism of ABLIM1 in osteoclast formation. These data demonstrated that ABLIM1 is a positive regulator of RANKL-mediated osteoclast formation via the modulation of the differentiation and PI3K/Akt/Rac1-dependent motility.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2777-2783
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• 2015

Background: Nestin is associated with neoplastic transformation. However, the mechanisms by which nestin contributes regarding invasion and malignancy of gastric adenocarcinoma (GAC) remain unknown. Recent studies have shown that the epithelial-mesenchymal transition (EMT) is important in invasion and migration of cancer cells. In the present study, we aimed to investigate the expression of nestin and its correlation with EMT-related proteins in GAC. Materials and Methods: The expression of nestin and EMT-related proteins was examined in GAC specimens and cell lines by immunohistochemistry and Western blotting. Clinicopathological features and survival outcomes were retrospectively analyzed. Results: Positive nestin immunostaining was most obviously detected in the cytoplasm, nucleus or both cytoplasm and nucleus of tumor cells in 19.2% (24/125) of GAC tissues, which was significantly higher than that in normal gastric mucosa tissues (1.7%, 1/60) (p=0.001). Nestin expression was closely related to several clinicopathological factors and EMT-related proteins (E-cadherin, vimentin and Snail) and displayed a poor prognosis. Interestingly, simultaneous cytoplasmic and nuclear nestin expression correlated with EMT-related proteins (E-cadherin, vimentin and Snail) (p<0.05) and lymph node metastasis (p=0.041) and a shorter survival time (p<0.05), but this was not the case with cytoplasmic or nuclear nestin expression. Conclusions: Nestin, particularly expression in both cytoplasm and nucleus, might be involved in regulating EMT and malignant progression in GAC, with potential as an unfavorable indicator in tumor diagnosis and a target for clinical therapy.

• Plant Biotechnology Reports
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• v.3 no.4
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• pp.309-315
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• 2009

Molecular markers developed from the flanking sequences of two cytoplasmic male sterility (CMS)-associated genes, orf456 and ${\Psi}atp6-2$, have been used for marker-assisted selection of CMS in pepper. However, in practice, the presence of orf456 and ${\Psi}atp6-2$ at substoichiometric levels even in maintainer lines hampers reliable selection of plants containing the CMS gene. In this study, we developed a novel CMS-specific molecular marker, accD-U, for reliable determination of CMS lines in pepper, and used the newly and previously developed markers to determine the cytoplasm types of pepper breeding lines and germplasms. This marker was developed from a deletion in a chloroplast-derived sequence in the mitochondrial genome of a CMS pepper line. CMS pepper lines could be unambiguously determined by presence or absence of the accD-U marker band. Application of orf456, ${\Psi}atp6-2$and accD-U to various pepper breeding lines and germplasms revealed that accD-U is the most reliable CMS selection marker. A wide distribution of orf456, but not ${\Psi}atp6-2$, in germplasms suggests that the pepper cytoplasm containing both orf456 and ${\Psi}atp6-2$ has been selected as CMS cytoplasm from cytoplasm containing only orf456. Furthermore, factors other than orf456 may be required for the regulation of male sterility in pepper.

• IMMUNE NETWORK
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• v.11 no.4
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• pp.216-222
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• 2011

Background: The ligand for CD137 (CD137L; also called 4-1BBL) is mainly expressed on activated APCs such as dendritic cells, B cells and macrophages. Even though CD137L functions as a trigger of the CD137 signaling pathway for T cell activation and expansion, engagement of CD137L can deliver a signal leading to the production of proinflammatory cytokines in macrophages. Methods: We generated cell-permeable TAT-CD137L cytoplasmic domain fusion protein (TAT-CD137Lct) and examined its ability to initiate the CD137L reverse signaling pathway. Results: Treatment of TAT-CD137Lct induced the production of high levels of IL-6 and TNF-${\alpha}$ mRNAs and proteins in peritoneal macrophages. TAT-CD137Lct increased phosphorylation of Erk, p38 MAPK and Jnk, and activated transcription factors C/EBP and CREB. However, TAT-CD137Lct did not visibly affect the degradation of the inhibitor of NF-${\kappa}B$ ($IkB{\alpha}$). We further demonstrated that JNK activation was required for TAT-CD137Lct-induced production of TNF-${\alpha}$, while activation of Erk and p38 MAPK were involved in IL-6 and TNF-${\alpha}$ production. Conclusion: Our results suggest that TATCD137Lct is an effective activator for the CD137L reverse signaling pathway.

• Journal of Gastric Cancer
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• v.15 no.1
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• pp.39-45
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• 2015

Purpose: Recent studies have revealed recurrent alterations in the cell adhesion gene FAT4, a candidate tumor suppressor gene, in cancer. FAT atypical cadherin 4 (FAT4) is a transmembrane receptor involved in the Hippo signaling pathway, which is involved in the control of organ size. Here, we investigated the loss of FAT4 expression and its association with clinicopathological risk factors in gastric cancer. Materials and Methods: We assessed the expression of FAT4 by using immunohistochemistry on three tissue microarrays containing samples from 136 gastric cancer cases, radically resected in the Soonchunhyang University Cheonan Hospital between July 2006 and June 2008. Cytoplasmic immunoexpression of FAT4 was semi-quantitatively scored using the H-score system. An H-score of ${\geq}10$ was considered positive for FAT4 expression. Results: Variable cytoplasmic expressions of FAT4 were observed in gastric cancers, with 33 cases (24.3%) showing loss of expression (H-score <10). Loss of FAT4 expression was associated with an increased rate of perineural invasion (H-score <10 vs. ${\geq}10$, 36.4% vs. 16.5%, P=0.015), high pathologic T stage (P=0.015), high tumor-node-metastasis stage (P=0.017), and reduced disease-free survival time (H-score <10 vs. ${\geq}10$, mean survival $62.7{\pm}7.3$ months vs. $79.1{\pm}3.1$ months, P=0.025). However, no association was found between the loss of FAT4 expression and tumor size, gross type, histologic subtype, Lauren classification, lymphovascular invasion, or overall survival. Conclusions: Loss of FAT4 expression appears to be associated with invasiveness in gastric cancer.

• Journal of Life Science
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• v.9 no.2
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• pp.52-56
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• 1999

The Raf, a cytoplasmic serine/thereonine protein kinase, acts as an important mediator of signals involving cell proliferation, differentiation and development. Multiple regulatory elements should participate in the expression of D-raf, Drosophila homolog of human c-raf-1. In order to search regulatory factors involved in the D-raf promoter activation, we accomplished the yeast one-hybrid screening using D-raf promoter region from bp-330 to -309 with respect to the transcription initiation site as bait. After screening, sixteen independent positive clones of ${\beta}$-galactosidase activties were identified and sequenced. Two clones having 94-98% identity with daughterless and one clone having 93% identity with escargot by Blast search among these clones were screened.

• Proceedings of the Korean Society of Embryo Transfer Conference
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• 2002.11a
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• pp.37-42
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• 2002

In ascidians, a primitive chordate, maternal cytoplasmic factors and inductive interactions are involved in the specification of cell fate in early embryos. The larval structure of ascidians is relatively simple, and the major mesodermal tissues of the tadpole larva are notochord, muscle and mesemchyme. Formation of muscle cells is a cell-autonomous process, and localized maternal macho-1 mRNA specify muscle fate in the posterior marginal zone of the early embryo. In contrast, inductive influence from endoderm precursors plays important roles in the specification of notochord and mesenchyme fates. FGF-Ras-MAPK signaling is involved in the induction of both tissues. The difference in responsiveness of the posterior mesenchyme and anterior notochord precursors is caused by the presence or absence of the posterior-vegetal egg cytoplasm, respectively. In these cases, directed signal may polarizes the responding cells and cause asymmetric cell divisions that operate in both the anterior and posterior regions.

• BMB Reports
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• v.52 no.7
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• pp.415-423
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• 2019

Signal transducer and activator of transcription 3 (STAT3) is a cytoplasmic transcription factor that regulates cell proliferation, differentiation, apoptosis, angiogenesis, inflammation and immune responses. Aberrant STAT3 activation triggers tumor progression through oncogenic gene expression in numerous human cancers, leading to promote tumor malignancy. On the contrary, STAT3 activation in immune cells cause elevation of immunosuppressive factors. Accumulating evidence suggests that the tumor microenvironment closely interacts with the STAT3 signaling pathway. So, targeting STAT3 may improve tumor progression, and anti-cancer immune response. In this review, we summarized the role of STAT3 in cancer and the tumor microenvironment, and present inhibitors of STAT3 signaling cascades.

• Journal of Veterinary Clinics
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• v.21 no.2
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• pp.219-228
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• 2004

Heart diseases related to conduction system can be occurred by primary defects in conduction system and by secondary to morphological heart diseases or drug toxicities. Multiple molecular defects responsible for arrhythmogenesis, including mutations in ion channels, cytoplasmic ion-channel-interacting proteins, gap-junction proteins, transcription factors and a kinase subunit, were found to be associated with the aetiology of primary cardiac conduction defects, especially inherited form. Despite a big progress in unveiling human arrhythmogenesis, conduction defects in dog has not been well studied except sudden death syndrome in German shepherd. In this review, molecular genetics in cardiac arrhythmogenesis, inherited human diseases associated with conduction defects and similar diseases in dogs will be discussed.

• Reproductive and Developmental Biology
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• v.39 no.2
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• pp.37-41
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• 2015

The oocyte undergoes various events during maturation and requires many substances for the maturation process. Various intracellular organelles are also involved in maturation of the oocyte. During the process glucose is essential for nuclear and cytoplasmic maturation, and adenosine triphosphate is needed for reorganization of the organelles and cytoskeleton. If mitochondrial function is lost, several developmental defects in meiotic chromosome segregation and maturation cause fertilization failure. The endoplasmic reticulum, a store for $Ca^{2+}$, releases $Ca^{2+}$ into the cytoplasm in response to various cellular signaling molecules. This event stimulates secretion of hormones, growth factors and antioxidants in oocyte during maturation. Also, oocyte nuclear maturation is stimulated by growth factors such as epidermal growth factor. This review summarizes roles of organelles with focus on the Golgi apparatus during maturation in oocyte.