• Molecules and Cells
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• v.22 no.2
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• pp.146-153
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• 2006

Cell polarity is critical for the division, differentiation, migration, and signaling of eukaryotic cells. RAX2 of budding yeast encodes a membrane protein localized at the cell cortex that helps maintain the polarity of the bipolar pattern. Here, we designate SPAC6f6.06c as $rax2^+$ of Schizosaccharomyces pombe, based on its sequence homology with RAX2, and examine its function in cell polarity. S. pombe $rax2^+$ is not essential, but ${\Delta}rax2$ cells are slightly smaller and grow slower than wild type cells. During vegetative growth or arrest at G1 by mutation of cdc10, deletion of $rax2^+$ increases the number of cells failing old end growth just after division. In addition, this failure of old end growth is dramatically increased in ${\Delta}tea1{\Delta}rax2$, pointing to genetic interaction of $rax2^+$ with $tea1^+$. ${\Delta}rax2$ cells contain normal actin and microtubule cytoskeletons, but lack actin cables, and the polarity factor for3p is not properly localized at the growing tip. In ${\Delta}rax2$ cells, and endogenous rax2p is localized at the cell cortex of growing cell tips in an actin- and microtubule-dependent manner. However, ${\Delta}rax2$ cells show no defects in cell polarity during shmoo formation and conjugation. Taken together, these observations suggest that rax2p controls the cell polarity of fission yeast during vegetative growth by regulating for3p localization.

• Journal of Life Science
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• v.21 no.5
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• pp.621-626
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• 2011

AMP-activated protein kinase (AMPK), a heterotrimeric complex comprising a catalytic ${\alpha}$ subunit and regulatory ${\beta}$ and ${\gamma}$ subunits, has been primarily studied as a major metabolic regulator in various organisms, but recent genetic studies discover its novel physiological functions. The first animal model with no functional AMPK ${\gamma}$ subunit gene was generated by using Drosophila genetics. AMPK ${\gamma}$ flies demonstrated lethality with severe defects in cuticle formation. Further histological analysis found that deletion of AMPK ${\gamma}$ causes severe defects in cell polarity in embryo epithelia. The phosphorylation of nonmuscle myosin regulatory light chain (MRLC), a critical regulator of epithelial cell polarity, was also diminished in AMPK ${\gamma}$ embryo epithelia. These defects in AMPK ${\gamma}$ mutant epithelia were successfully restored by over-expression of AMPK ${\gamma}$. Collectively, these results suggested that AMPK ${\gamma}$ is a critical cell polarity regulator in metazoan development.

• Journal of Microbiology
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• v.44 no.3
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• pp.311-319
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• 2006

Bud6p is a component of a polarisome that controls cell polarity in Saccharomyces cerevisiae. In this study, we investigated the role of the Candide albicans Bud6 protein (CaBud6p) in cell polarity and hyphal development. CaBud6p, which consists of 703 amino acids, had 37% amino-acid sequence identity with the Bud6 protein of S. cerevisiae. The homozygous knock-out of CaBUD6 resulted in several abnormal phenotypes, such as a round and enlarged cells, widened bud necks, and a random budding pattern. In hypha-inducing media, the mutant cells had markedly swollen tips and a reduced ability to switch from yeast to hypha. In addition, a yeast two-Hybrid analysis showed a physical interaction between CaBud6p and CaAct1p, which suggests that CaBud6p may be involved in actin cable organization, like Bud6p in S. cerevisiae. Taken together, these results indicate that CaBud6 plays an important role in the polarized growth of C. albicans.

• Biomolecules & Therapeutics
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• v.32 no.3
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• pp.291-300
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• 2024

Autosomal dominant polycystic kidney disease (ADPKD), a congenital genetic disorder, is a notable contributor to the prevalence of chronic kidney disease worldwide. Despite the absence of a complete cure, ongoing research aims for early diagnosis and treatment. Although agents such as tolvaptan and mTOR inhibitors have been utilized, their effectiveness in managing the disease during its initial phase has certain limitations. This review aimed to explore new targets for the early diagnosis and treatment of ADPKD, considering ongoing developments. We particularly focus on cell polarity, which is a key factor that influences the process and pace of cyst formation. In addition, we aimed to identify agents or treatments that can prevent or impede the progression of renal fibrosis, ultimately slowing its trajectory toward end-stage renal disease. Recent advances in slowing ADPKD progression have been examined, and potential therapeutic approaches targeting multiple pathways have been introduced. This comprehensive review discusses innovative strategies to address the challenges of ADPKD and provides valuable insights into potential avenues for its prevention and treatment.

• Molecules and Cells
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• v.44 no.3
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• pp.168-178
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• 2021

The retinal pigment epithelium (RPE) forms a monolayer sheet separating the retina and choroid in vertebrate eyes. The polarized nature of RPE is maintained by distributing membrane proteins differentially along apico-basal axis. We found the distributions of these proteins differ in embryonic, post-natal, and mature mouse RPE, suggesting developmental regulation of protein trafficking. Thus, we deleted tumor susceptibility gene 101 (Tsg101), a key component of endosomal sorting complexes required for transport (ESCRT), in embryonic and mature RPE to determine whether ESCRT-mediated endocytic protein trafficking correlated with the establishment and maintenance of RPE polarity. Loss of Tsg101 severely disturbed the polarity of RPE, which forms irregular aggregates exhibiting non-polarized distribution of cell adhesion proteins and activation of epidermal growth factor receptor signaling. These findings suggest that ESCRT-mediated protein trafficking is essential for the development and maintenance of RPE cell polarity.

• BMB Reports
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• v.43 no.2
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• pp.69-78
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• 2010

Asymmetric cell division is a fundamental mechanism for the generation of body axes and cell diversity during early embryogenesis in many organisms. During intrinsically asymmetric divisions, an axis of polarity is established within the cell and the division plane is oriented to ensure the differential segregation of developmental determinants to the daughter cells. Studies in the nematode Caenorhabditis elegans have contributed greatly to our understanding of the regulatory mechanisms underlying cell polarity and asymmetric division. However, much remains to be elucidated about the molecular machinery controlling the spatiotemporal distribution of key components. In this review we discuss recent findings that reveal intricate interactions between translational control and targeted proteolysis. These two mechanisms of regulation serve to carefully modulate protein levels and reinforce asymmetries, or to eliminate proteins from certain cells.

• BMB Reports
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• v.51 no.9
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• pp.425-426
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• 2018

As highly conserved signaling cascades of multicellular organisms, Wnt and Hippo pathways control a wide range of cellular activities, including cell adhesion, fate determination, cell cycle, motility, polarity, and metabolism. Dysregulation of those pathways are implicated in many human diseases, including cancer. Similarly to ${\beta}-catenin$ in the Wnt pathway, the YAP transcription co-activator is a major player in Hippo. Although the intracellular dynamics of YAP are well-known to largely depend on phosphorylation by LATS and AMPK kinases, the molecular effector of YAP cytosolic translocation remains unidentified. Recently, we reported that the Dishevelled (DVL), a key scaffolding protein between canonical and non-canonical Wnt pathway, is responsible for nuclear export of phosphorylated YAP. The DVL is also required for YAP intracellular trafficking induced by E-cadherin, ${\alpha}-catenin$, or metabolic stress. Note that the p53/LATS2 and LKB1/AMPK tumor suppressor axes, commonly inactivated in human cancer, govern the reciprocal inhibition between DVL and YAP. Conversely, loss of the tumor suppressor allows co-activation of YAP and Wnt independent of epithelial polarity or contact inhibition in human cancer. These observations provide novel mechanistic insight into (1) a tight molecular connection merging the Wnt and Hippo pathways, and (2) the importance of tumor suppressor contexts with respect to controlled proliferation and epithelial polarity regulated by cell adhesion.

• Korean Chemical Engineering Research
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• v.58 no.1
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• pp.122-126
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• 2020

In this study, we produced the micropatterned channel system using polydimethylsiloxane (PDMS) and micromolding in capillaries (MIMIC) technology and evaluated cellular polarity signals through high-resolved imaging at the single-cell level. In cells treated with platelet-derived growth factor (PDGF), three types of key signals in cell migration; phosphoinositide 3-kinase (PI3 K), Rac, and Actin, were strongly activated in the front area compared to the rear region, whereas myosin light chain (MLC) showed no notable activity in the front and rear areas. Our results will, therefore, provide important information and methodology for studying the correlation between cell polarity signals and cell migration under the newly defined microenvironment.

• Journal of Life Science
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• v.23 no.8
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• pp.970-977
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• 2013

The epithelial-to-mesenchymal transition (EMT) plays an essential role in embryogenesis and is involved in tumor metastasis and invasion; it significantly contributes to tumor progression and aggressiveness. The EMT is characterized by a loss of epithelial cell polarity as a result of the reduced expression of epithelial E-cadherin, a hallmark of the EMT, and the acquisition of mesenchymal-like cell morphology. Reactive oxygen species (ROS) such as $O_2{^-}$, $H_2O_2$, and $OH^-$ have been demonstrated to induce the EMT; although Snail is involved in ROS-induced EMT by transcriptionally repressing E-cadherin, its mechanism is not fully understood. In this study, we examined the effects of early growth response 1 (Egr-1) overexpression in noninvasive breast tumor cell line MCF-7 cells. Upon Egr-1 overexpression, MCF-7 cells lost epithelial cell polarity and became more spindle-shaped, indicating that Egr-1 may induce EMT. We found that Snail is implicated in Egr-1 induced EMT. We further demonstrate that the Egr-1-Snail axis is activated by ROS and plays a critical role(s) in ROS-induced EMT.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.31 no.1 s.49
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• pp.43-49
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• 2005

Recently, according as people who have sensitive skin increase, we've been giving more importance to the safety of cosmetics. Especially, preservative is known to be one of the main stimuli which cause side-effects of cosmetics. However, there have been few reports describing cell cytotoxicity, skin penetration, oil-aqueous phase partition, anti-microbial activity of preservatives and their correlation with skin irritation. The study is aimed to develop low irritable preservative system with phenoxyethanol, one of the most commonly used preservatives in cosmetics, considering various factors mentioned above. According to our results of cell cytotoxicity against human normal fibroblasts by means of MTT assay, phenoxyethanol showed the lowest cytotoxicity when compared to other preservatives tested (cytotoxicity: pro-pylparaben > butylparaben > ethylparaben > methylparaben > triclosan > phenoxyethanol), but human patch test for assessing shin primary irritation revealed that phenoxyethanol has higher skin irritation than methylparaben and triclosan. We performed in vitro skin penetration test using horizontal Franz diffusion cells with skin membrane prepared from hairless mouse (5 ${\~}$ 8 weeks, male) to evaluate the rate of skin penetration of preservatives. From the results, we found that the higher irritable property of phenoxyethanol in human skin correlates with its predominant permeability (skin penetration: phenoxyethanol > methylparaben > ethylparaben > propylparaben > butylfaraben > triclosan). Therefore, we made an effort to reduce skin permeability of phenoxyethanol and found that not only the rate of skin penetration of phenoxyethanol but also its skin irritation is dramatically reduced in formulas containing oils with low polarity. In the experiments to investigate the effect of oil polarity on the oil-aqueous phase partition of phenoxyethanol, more than $70\%$ of phenoxyethanol was partitioned in aqueous phase in formulas containing oils with low polarity, while about $70 {\~} 90\%$ of phenoxyethanol was partitioned in oil phase in formulas containing oils with high polarity. Also, in aqueous phase phenoxyethanol showed greater anti-microbial activity. Conclusively, it appears that we can develop less toxic preservative system with reduced use dosage of phenox-yethanol and its skin penetration by changing oil composition in formulas.