• Title/Summary/Keyword: Dishevelled

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Secondary Structure, 1H, 13C and 15N Resonance Assignments and Molecular Interactions of the Dishevelled DIX Domain

  • Capelluto, Daniel G.S.;Overduin, Michael
    • BMB Reports
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    • v.38 no.2
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    • pp.243-247
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    • 2005
  • Dishevelled (Dvl) is a positive regulator of the canonical Wnt signaling pathway, which regulates the levels of $\beta$-catenin. The $\beta$-catenin oncoprotein depends upon the association of Dvl and Axin proteins through their DIX domains, and its accumulation directs the expression of specific developmental-related genes at the nucleus. Here, the $^1H$, $^{13}C$, and $^{15}N$ resonances of the human Dishevelled 2 DIX domain are assigned using heteronuclear nuclear magnetic resonance (NMR) spectroscopy. In addition, helical and extended elements are identified based on the NMR data. The results establish a structural context for characterizing the actin and phospholipid interactions and binding sites of this novel domain, and provide insights into its role in protein localization to stress fibers and cytoplasmic vesicles during Wnt signaling.

Dishevelling Wnt and Hippo

  • Kim, Nam Hee;Lee, Yoonmi;Yook, Jong In
    • 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.

A Study on Psychological Function of Mourning Ceremonial Dresses in Confucianism (유교 상례복의 심리적 기능에관한 연구)

  • 조우현
    • Journal of the Korean Home Economics Association
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    • v.32 no.4
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    • pp.233-240
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    • 1994
  • The purpose of this study is to consider psycological funtions of mourning dresses in Confucianism. By each step of A.V.Gennep's passage rites, the result of this thesis summarised as follow; In the first Seperation rites after calling the death' name three times the relatives for whom mourning is due become dishevelled hair bare feet and bare shoulder etc. In the second Transition rites, bereaved familly has worn 5 class mourning dresses in deep grief. In the third Cooperation rites, gradually the living familly goes through three year stages of changing mourning dresses to ordinary colthes. In Confucian funeral ceremony the deviation of clothing behavior in each mourning step sublimates bereaved person's sorrow into their internal security.

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RNF152 negatively regulates Wnt/β-catenin signaling in Xenopus embryos

  • Yoon, Gang-Ho;Kim, Kyuhee;Park, Dong-Seok;Choi, Sun-Cheol
    • BMB Reports
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    • v.55 no.5
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    • pp.232-237
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    • 2022
  • The Wnt/β-catenin signaling plays crucial roles in early development, tissue homeostasis, stem cells, and cancers. Here, we show that RNF152, an E3 ligase localized to lysosomes, acts as a negative regulator of the Wnt/β-catenin pathway during Xenopus early embryogenesis. Overexpression of wild-type (WT) RNF152 inhibited XWnt8-induced stabilization of β-catenin, ectopic expression of target genes, and activity of a Wnt-responsive promoter. Likewise, an E3 ligase-defective RNF152 had repressive effects on the Wnt-dependent gene responses but not its truncation mutant lacking the transmembrane domain. Conversely, knockdown of RNF152 further enhanced the transcriptional responses induced by XWnt8. RNF152 morphants exhibited defects in craniofacial structures and pigmentation. In line with this, the gain-of-RNF152 function interfered with the expression of neural crest (NC) markers, whereas its depletion up-regulated NC formation in the early embryo. Mechanistically, RNF152 inhibits the polymerization of Dishevelled, which is key to Wnt signaling, in an E3 ligase-independent manner. Together, these results suggest that RNF152 controls negatively Wnt/β-catenin signaling to fine-tune its activity for NC formation in Xenopus embryo.

CKD-581 Downregulates Wnt/β-Catenin Pathway by DACT3 Induction in Hematologic Malignancy

  • Kim, Soo Jin;Kim, Suntae;Choi, Yong June;Kim, U Ji;Kang, Keon Wook
    • Biomolecules & Therapeutics
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    • v.30 no.5
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    • pp.435-446
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    • 2022
  • The present study evaluated the anti-cancer activity of histone deacetylase (HDAC)-inhibiting CKD-581 in multiple myeloma (MM) and its pharmacological mechanisms. CKD-581 potently inhibited a broad spectrum of HDAC isozymes. It concentration-dependently inhibited proliferation of hematologic cancer cells including MM (MM.1S and RPMI8226) and T cell lymphoma (HH and MJ). It increased the expression of the dishevelled binding antagonist of β-catenin 3 (DACT3) in T cell lymphoma and MM cells, and decreased the expression of c-Myc and β-catenin in MM cells. Additionally, it enhanced phosphorylated p53, p21, cleaved caspase-3 and the subG1 population, and reversely, downregulated cyclin D1, CDK4 and the anti-apoptotic BCL-2 family. Finally, administration of CKD-581 exerted a significant anti-cancer activity in MM.1S-implanted xenografts. Overall, CKD-581 shows anticancer activity via inhibition of the Wnt/β-catenin signaling pathway in hematologic malignancies. This finding is evidence of the therapeutic potential and rationale of CKD-581 for treatment of MM.

Expression of DDR1 and DVL1 in Invasive Ductal and Lobular Breast Carcinoma does not Correlate with Histological Type, Grade and Hormone Receptor Status

  • Ameli, Fereshteh;Rose, Isa Mohd;Masir, Noraidah
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.6
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    • pp.2385-2390
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    • 2015
  • Background: Invasive ductal (IDC) and lobular (ILC) carcinomas are the common histological types of breast carcinoma which are difficult to distinguish when poorly differentiated. Discoidin domain receptor (DDR1) and Drosophila dishevelled protein (DVL1) were recently suggested to differentiate IDC from ILC. Objectives: To assess the expression of DDR1 and DVL1 and their association with histological type, grading and hormonal status of IDC and ILC. Materials and Methods: This cross sectional study was conducted on IDC and ILC breast tumours. Tumours were immunohistochemically stained for (DDR1) and (DVL1) as well as estrogen receptor (ER), progesterone receptor (PR) and C-erbB2 receptor. Demographic data including age and ethnicity were obtained from patient records. Results: A total of 51 cases (30 IDCs and 21 ILCs) were assessed. DDR1 and DVL1 expression was not significantly associated with histological type (p=0.57 and p=0.66 respectively). There was no association between DDR1 and DVL1 expression and tumour grade (p=0.32 and p=1.00 respectively), ER (p=0.62 and 0.50 respectively), PR (p=0.38 and p=0.63 respectively) and C-erbB2 expression (p=0.19 and p=0.33 respectively) in IDC. There was no association between DDR1 and DVL1 expression and tumour grade (p=0.52 and p=0.33 respectively), ER (p=0.06 and p=0.76 respectively), PR (p=0.61 and p=0.43 respectively) and C-erbB2 expression (p=0.58 and p=0.76 respectively) in ILC. Conclusions: This study revealed that DDR1 and DVL1 are present in both IDC and ILC regardless of the tumour differentiation. More studies are needed to assess the potential of these two proteins in distinguishing IDC from ILC in breast tumours.

Study on the Changes of Men's Hair Styles of Japan - from Ancient to Modern - (일본 남성의 헤어스타일 변천에 관한 연구 - 고대에서 근대까지 -)

  • Jo, Ki-Yeu;Jung, Yeon
    • Fashion & Textile Research Journal
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    • v.3 no.4
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    • pp.337-343
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    • 2001
  • This study was purposed to see how men's hair styles of Japan had changed throughout history and results of the study was as follows. There are such evidences as topknots in its primitive styles and wooden combs that several hair styles were tried already in the primitive Jomon Period. In the Yayoi period, bare topknot style without crowns and Mizura style in which hair drop down both ears were popular. In the period of ancient burial mounds, Mizura style was dominative style and varied its form and shape according to classes and status. In the Aska and Nara era, topknot-in-the-crown style in which hair bound in one as in continental style and put in crown or hood, which style was influenced by the Sui and the Tang periods of China. Since the Heian period, topknot-in-the-Ebosi style, binding style, and Karawa style as well as topknot-in-the-crown style came in sight and Sakayaki style became popular in the Kamakura and Muromachi periods. In the Momoyama period, Chasenmage style and Ichomage style were spread widely. In the early Edo era, Wakashumage style and Yaromage style as well as Ichomage style were preferred. In the middle of Edo era in which form and shape of topknot was more distinct symbol of class, status and job than in any other period, Tachmach style under the influence of the Punkin and Honda modes. Sonno style was popular in the late Edo era. There was a drastic disappearance of topknot style by the hair-cutting order during the Meiji Restoration period and civilized hair style of the Jankiri style, a kind of dishevelled hair style without making a topknot was in fashion and continued to the present.

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