DIRECT EVIDENCE FOR A ROLE OF β-CATENIN/LEF-1 SIGNALING PATHWAY IN INDUCTION OF EMT

KIM, KWONSEOP,LU, ZIFAN,HAY, ELIZABETH D. 전남대학교 약품개발연구소 2002 약품개발연구지 Vol.11 No.-

Epithelial-mesenchymal transformation (EMT) is an important process in development that is characterized by loss of E-cadherin, β-catenin relocalization, and acquisition of elongated cell shape and ability to invade ECM. β-catenin has been shown to activate LEF-1 transcription during EMT induced in vitro by c-Fos. Here, we ask whether or not LEF-1 directly introduced into epithelial cells in an adenovirus construct can in duce EMT. In normal epithelial cell lines, such as HCE and MDSK cells, that contain functional APC, nuclear β-catenin induced by exogenous LEF-1 is rapidly exported and EMT is not induced. Leptomycin-B blocks β-catenin nuclear export, but no EMT occurs due to toxicity. Addition of Wnt-1 to normal epithelial cell lines stabilizes cytoplasmic β-catenin that LEF-1 then transports to nuclei, causing a small amount of EMT. Our experiments demonstrated, however, that overexpressed LEF-1 upregulates nuclear β-catenin and promotes dramatic EMT in DLD-1 epithelial tumors that retain nuclear β-catenin. This EMT is reversible if the LEF-1 virus is removed. Thus, our results demonstrate that LEF-1 can induce EMT directly when its transcription activity is activated by stable nuclear β-catenin. Normal epithelial cells appear to use APC to keep β-cathnin out of the nucleus, thereby avoiding pathologies such as metastases due to LEF/β-catenin-induced EMT.

항공화물 보세창고의 화물 저장법과 이송 장비 운영의 효율성 개선

송권섭(Kwonseop Song),이후언(Huun Lee),채준재(Junjae Chae) 한국산업경영시스템학회 2009 한국산업경영시스템학회지 Vol.32 No.1

A bonded warehouse is the warehouse located in bonded area. It functions not only as a general warehouse but also as a place for managing the work related to import and export bonded goods. As a general warehouse, it uses the rack system to store the goods and the folk lift truck to move the unitized goods. The operation of the storing system closely related to the efficiency of space uses in a warehouse and vehicle working. Thus, vehicle performance measured in distance units in the warehouse could be used as one of the key performance measure in warehouse system. This paper focuses on the operation efficiency of the bonded warehouse which uses rack system for the storing and the folk lift truck for moving goods. The method of load allocation for balancing the rack uses and vehicle operation for maximizing efficiency are the specific concerns in this paper. The simulation study is conducted to find a policy for efficient vehicle operation based on balanced rack utilization, and the favorable result for the system operation would lead the usable proposal in vehicle operation.

Role of β-Catenin/LEF in Tumorigenesis

Kim, Kwonseop 전남대학교 약품개발연구소 2001 약품개발연구지 Vol.10 No.-

TYROSINE PHOSPHORYLATION TRANSLOCATES β-CATENIN FROM CELL-CELL INTERFACE TO THE CYTOPLASM, BUT DOES NOT SIGNIFICANTLY ENHANCE THE LEF-1-DEPENDENT TRANSACTIVATING FUNCTION

Kim, KWONSEOP,Lee, Kwang-Youl 전남대학교 약품개발연구소 2001 약품개발연구지 Vol.10 No.-

β-catenin plays an essential role in cells, not only as a cadherin-associated complex, but also as a signaling molecule in the nucleus. Tyrosine phosphorylation of β-catenin has been shown to correlate with tumorigenesis, cell migration, and developmental processes. However, its exact effects on downstream targets in the nucleus are not yet clear. In this study, we used HCT-15 colon carcinoma and NIH 3T3 fibroblasts as models to investigate the effects of a phosphotyrosine phosphatase (PTPase) inhibitor on the localization of β-catenin, the binding affinity to LEF-1 (Lymphoid Enhancer Factor), and on LEF-1-dependent transactivation function. Treatment with a PTPase inhibitor, pervanadate, increased the tyrosine phosphorylation of β-catenin in a time-dependent manner and led to its relocation from cell-cell interfaces to the cytoplasm. This phosphorylation/dephosphorylation of β-catenin does not require its presence at cell-cell interfaces. However, tyrosine phosphorylation of β-catenin does not change its binding affinity to LEF-l nor enhance cyclin D1 transactivation, a nuclear target of β-catenin/ LEF-l. This result suggests that tyrosine phosphorylation of β-catenin has effects on the binding to cadherins in the cytoplasm but not on its LEF-l-dependent transactivating function in the nucleus.

Dendrite-like Process Formation and Cytoskeletal Remodeling Regulated by δ-Catenin expression

Kim, Kwonseop,Sirota, Anna,Chen, Yan-hua,Jones, Shiloh B.,Dudek, Ronald,Lanford, George W.,Thakore, Chittam,Lu, Qun 전남대학교 약품개발연구소 2002 약품개발연구지 Vol.11 No.-

Actin- and microtubule-mediated changes in cell shape are essential for many cellular activities. However, the molecular mechanisms underlying the interplay between the two are complex and remain obscure. Here we show that the expression of δ-catenin (or NPRAP/Neurojungin), a member of p120^ctm subfamily of armadillo proteins can induce the branching of dendrite-like processes in 3T3 cells and enhance dendritic morphogenesis in primary hippocampal neurons. This induction of branching phenotype involves initially the disruption of filamentous actin, and requires the growth of microtubules. The carboxyl-terminal truncation mutant of δ-catenin can cluster and redistribute the full-length protein, and dominantly inhibit its branching effect. δ-Catenin forms protein complexes and can bind directly to actin in vitro. The carboxyl-terminal truncation of δ-catenin does not interfere with its actin-binding capability; therefore the actin interaction alone is not sufficient for the induction of dendrite-like processes. When δ-catenin-transformed cells establish elaborate dendrite-like branches, the main cellular processes become stabilized and resist the disruption od both actin filaments and microscopy and time-lapse recording analyses. We suggest that δ-catenin can effect a biphasic cytoskeletal remodeling event which differentially regulates actin and microtubules and promotes cellular morphogenesis.

NEW EVIDENCE THAT NUCLEAR IMPORT OF ENDOGENOUS β-CATENIN IS LEF-1 DEPENDENT, WHILE LEF-1 INDEPENDENT IMPORT OF EXOGENOUS β-CATENIN LEADS TO NUCLEAR ABNORMALITIES

Kim, KWONSEOP,Elizabeth D. Hay 전남대학교 약품개발연구소 2001 약품개발연구지 Vol.10 No.-

The once accepted idea that LEF- 1 transports β-catenin into nuclei has recently been challenged by experiments using exogenous β-catenin. Here, we investigated the effects of β-catenin and LEF-1 on nuclear import of β-catenin using different combinations of exogenous and endogenous molecules over longer lengths of time than previously studied. Nuclear β-catenin is not detectable in corneal fibroblasts and epithelia or NIH 3T3 and MDCK cells. In LEF-1 transfections, we show that the B-box of LEF-1 is required to move cytoplasmic endogenous β-catenin into the nuclei of such cells, proving that LEF-1 does transport endogenous β-catenin into nuclei. Moreover, transfection of uveal melanoma cells with B-box deficient LEF-1 inhibits nuclear import of β-catenin by endogenous LEF-1. However, the movement of overexpressed exogenous β-catenin into nuclei is unaffected by the presence or absence of LEF-l and forms abnormal nuclear aggregates that are a prelude to subsequent apoptosis. We conclude that nuclear transport of exogenous β-catenin independently of LEF-1 has questionable physiological significance.

항공화물 보세창고 운영의 효율성 개선

채준재(Junjae Chae),송권섭(Kwonseop Song),이후언(Huun Lee) 한국산업경영시스템학회 2008 한국산업경영시스템학회 학술대회 Vol.2008 No.하계

A bonded warehouse is the warehouse located in bonded area. It functions not only as a general warehouse but also as a place for managing the work related to import and export bonded goods. As a general warehouse, it uses the rack system to store the goods and the folk lift truck to move the unitized goods. The operation of the storing system closely related to the efficiency of space uses in a warehouse and vehicle working. Thus, vehicle performance measured in distance units in the warehouse could be used as one of the key performance measure in warehouse system. This paper focuses on the operation efficiency of the bonded warehouse which uses rack system for the storing and the folk lift truck for moving goods. The method of load allocation for balancing the rack uses and vehicle operation for maximizing efficiency are the specific concerns in this paper. The simulation study is conducted to find a policy for efficient vehicle operation based on balanced rack utilization, and the favorable result for the system operation would lead the usable proposal in vehicle operation.

δ-Catenin interacts with LEF-1 and negatively regulates its transcriptional activity.

He, Yongfeng,Ki, Hyunkyoung,Kim, Hangun,Kim, Kwonseop Published for the International Federation for Cel 2015 Cell biology international Vol.39 No.8

<P>δ-Catenin and β-catenin belong to different subfamilies of armadillo proteins but share some common binding partners, such as E-cadherin. This is the first study that demonstrated a novel common binding partner for δ-catenin and β-catenin, lymphoid enhancer factor-1 (LEF-1). We found that the N-terminus of δ-catenin (amino acids 85-325) bound to the middle region of LEF-1 unlike β-catenin. Overexpressed δ-catenin entered the nucleus and inhibited LEF-1-mediated transcriptional activity in Bosc23 and DLD-1 cell lines. The current study provided novel insights that will provide a better understanding of the effects of δ-catenin on Wnt/LEF-1-mediated transcriptional activity.</P>

WNK4 phosphorylates ser²⁰⁶ of claudin-7 and promotes paracellular Cl⁻ permeability

Tatum, Rodney,Zhang, Yuguo,Lu, Qun,Kim, Kwonseop,Jeansonne, Beverly G.,Chen, Yan-Hua North-Holland Pub 2007 FEBS letters Vol.581 No.20

<P><B>Abstract</B></P><P>Mutations in WNK4 have been linked to hypertension in PHAII. Paracellular ion transport has been reported to be involved in this disease process; however, the specific molecular target has not been identified. In this study, we found that TJ protein claudin-7 and WNK4 were partially co-localized in renal tubules of rat kidney and co-immunoprecipitated in kidney epithelial cells. The wild-type and PHAII-causing mutant, but not the kinase-dead mutant, phosphorylated claudin-7. We have identified ser<SUP>206</SUP> in the COOH-terminus of claudin-7 as a putative phosphorylation site for WNK4. More importantly, disease-causing mutant enhanced claudin-7 phosphorylation and significantly increased paracellular permeability to Cl<SUP>−</SUP>.</P>

Regulation of Notch1/NICD and Hes1 Expressions by GSK-3α/β

Yun Hye Jin,Hangun Kim,Minsoo Oh,Hyunkyung Ki,Kwonseop Kim 한국분자세포생물학회 2009 Molecules and cells Vol.27 No.1

Notch signaling is controlled at multiple levels. In particular, stabilized Notch receptor activation directly affects the transcriptional activations of Notch target genes. Although some progress has been made in terms of defining the regulatory mechanism that alters Notch stability, it has not been determined whether Notch1/NICD stability is regulated by GSK-3α. Here, we show that Notch1/NICD levels are significantly regulated by GSK-3β and by GSK-3α. Treatment with LiCl (a specific GSK-3 inhibitor) or the overexpression of the kinase-inactive forms of GSK-3α/β significantly increased Notch1/NICD levels. Endogenous NICD levels were also increased by either GSK-3α/β- or GSK-3α-specific siRNA. Furthermore, it was found that GSK-3α binds to Notch1. Deletion analysis showed that at least three Thr residues in Notch1 (Thr-1851, 2123, and 2125) are critical for its response to LiCl, which increased not only the transcriptional activity of endogenous NICD but also Hes1 mRNA levels. Taken together, our results indicate that GSK-3α is a negative regulator of Notch1/ NICD.