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https://www.readbyqxmd.com/read/28810742/determination-of-rate-limiting-factor-for-formation-of-beta-catenin-destruction-complexes-using-absolute-protein-quantification
#1
Masashi Kitazawa, Tomohisa Hatta, Koji Ogawa, Eriko Fukuda, Naoki Goshima, Tohru Natsume
Wnt/β-catenin signaling plays important roles in both ontogenesis and development. In the absence of a Wnt stimulus, β-catenin is degraded by a multiprotein "destruction complex" that includes Axin, APC, GSK3B, and FBXW11. Although the key molecules required for transducing Wnt signals have been identified, a quantitative understanding of this pathway has been lacking. Here, we calculated the absolute number of β-catenin destruction complexes by absolute protein quantification using LC-MS/MS. Similar amounts of destruction complex-constituting proteins and β-catenin interacted, and the number of destruction complexes was calculated to be about 1,468 molecules/cell...
August 15, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28800791/microrna-154-inhibits-the-growth-and-invasion-of-gastric-cancer-cells-by-targeting-dixdc1-wnt-signaling
#2
Jifu Song, Zhibin Guan, Maojiang Li, Sha Sha, Chao Song, Zhiwei Gao, Yongli Zhao
MicroRNAs (miRNAs) have emerged as pivotal regulators of the development and progression of gastric cancer. Studies have shown that miR-154 is a novel cancer-associated miRNA involved in various cancers. However, the role of miR-154 in gastric cancer remains unknown. Here we aimed to investigate the biological function and the potential molecular mechanism of miR-154 in gastric cancer. We found that miR-154 was significantly downregulated in gastric cancer tissues and cell lines. The overexpression of miR-154 significantly repressed the growth and invasion of gastric cancer cells...
August 11, 2017: Oncology Research
https://www.readbyqxmd.com/read/28798413/structural-basis-for-ccd1-auto-inhibition-in-the-wnt-pathway-through-homomerization-of-the-dix-domain
#3
Shin-Ichi Terawaki, Shohei Fujita, Takuya Katsutani, Kensuke Shiomi, Kazuko Keino-Masu, Masayuki Masu, Kaori Wakamatsu, Naoki Shibata, Yoshiki Higuchi
Wnt signaling plays an important role in governing cell fate decisions. Coiled-coil-DIX1 (Ccd1), Dishevelled (Dvl), and Axin are signaling proteins that regulate the canonical pathway by controlling the stability of a key signal transducer β-catenin. These proteins contain the DIX domain with a ubiquitin-like fold, which mediates their interaction in the β-catenin destruction complex through dynamic head-to-tail polymerization. Despite high sequence similarities, mammalian Ccd1 shows weaker stimulation of β-catenin transcriptional activity compared with zebrafish (z) Ccd1 in cultured cells...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28794794/sfrp2-enhances-the-osteogenic-differentiation-of-apical-papilla-stem-cells-by-antagonizing-the-canonical-wnt-pathway
#4
Luyuan Jin, Yu Cao, Guoxia Yu, Jinsong Wang, Xiao Lin, Lihua Ge, Juan Du, Liping Wang, Shu Diao, Xiaomeng Lian, Songlin Wang, Rui Dong, Zhaochen Shan
BACKGROUND: Exploring the molecular mechanisms underlying directed differentiation is helpful in the development of clinical applications of mesenchymal stem cells (MSCs). Our previous study on dental tissue-derived MSCs demonstrated that secreted frizzled-related protein 2 (SFRP2), a Wnt inhibitor, could enhance osteogenic differentiation in stem cells from the apical papilla (SCAPs). However, how SFRP2 promotes osteogenic differentiation of dental tissue-derived MSCs remains unclear...
2017: Cellular & Molecular Biology Letters
https://www.readbyqxmd.com/read/28772205/anti-proliferative-activity-of-cgk012-against-multiple-myeloma-cells-via-wnt-%C3%AE-catenin-signaling-attenuation
#5
Pyung Jun Choi, Yuseok O, Jin-Hyuk Her, Eunju Yun, Gyu Yong Song, Sangtaek Oh
The aberrant activation of Wnt/β-catenin signaling is involved in the development of multiple myeloma; thus, this signaling pathway is a potential target for the development of therapeutics for this malignancy. Here, we performed cell-based chemical screening and found that CGK012, a pyranocoumarin compound, suppressed the Wnt3a-CM-mediated activation of β-catenin response transcription. CGK012 induced β-catenin phosphorylation at Ser33/Ser37/Thr41, leading to proteasomal degradation and reducing the level of intracellular β-catenin...
July 22, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28770488/identification-and-characterization-of-functional-single-nucleotide-polymorphisms-snps-in-axin-1-gene-a-molecular-dynamics-approach
#6
Imran Khan, Irfan A Ansari, Pratichi Singh, J Febin Prabhu Dass, Fahad Khan
Wnt signaling pathway has been reported to play crucial role in intestinal crypt formation and deregulation of this pathway is responsible for colorectal cancer initiation and progression. Axin 1, a scaffold protein, play pivotal role in the regulation of Wnt/β-catenin signaling pathway and has been found to be mutated in several cancers; primarily in colon cancer. Considering its crucial role, a structural and functional analysis of missense mutations in Axin 1 gene was performed in this study. Initially, one hundred non-synonymous single nucleotide polymorphisms in the coding regions of Axin 1 gene were selected for in silico analysis...
August 2, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28741966/the-connections-of-wnt-pathway-components-with-cell-cycle-and-centrosome-side-effects-or-a-hidden-logic
#7
Vítězslav Bryja, Igor Červenka, Lukáš Čajánek
Wnt signaling cascade has developed together with multicellularity to orchestrate the development and homeostasis of complex structures. Wnt pathway components - such as β-catenin, Dishevelled (DVL), Lrp6, and Axin-- are often dedicated proteins that emerged in evolution together with the Wnt signaling cascade and are believed to function primarily in the Wnt cascade. It is interesting to see that in recent literature many of these proteins are connected with cellular functions that are more ancient and not limited to multicellular organisms - such as cell cycle regulation, centrosome biology, or cell division...
July 25, 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28731177/co%C3%A2-expression-of-axin-and-apc-gene-fragments-inhibits-colorectal-cancer-cell-growth-via-regulation-of-the-wnt-signaling-pathway
#8
Meili Xu, Xianling Liu, Yan Xu, Shicong Zhu, Yawen Gao
Adenomatous polyposis coli (APC) and Axin interactions serve an important role in colorectal cancer (CRC) pathogenesis. The aim of the present study was to assess the combined effects of Axin and APC co‑expression in CRC cells, and to determine the underlying mechanisms involved. SW480 cells were divided into the following groups: Untransfected (SW480 group), transfected with pEGFP‑N3plus pCS2‑MT (SW480/vector‑vector), transfected with pEGFP‑N3‑APC5 (SW480/APC5), and transfected with pEGFP‑N3‑APC5 pluspCS2‑MT‑Axin (SW480/APC5‑Axin)...
July 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28723898/fructose-1-6-bisphosphate-and-aldolase-mediate-glucose-sensing-by-ampk
#9
Chen-Song Zhang, Simon A Hawley, Yue Zong, Mengqi Li, Zhichao Wang, Alexander Gray, Teng Ma, Jiwen Cui, Jin-Wei Feng, Mingjiang Zhu, Yu-Qing Wu, Terytty Yang Li, Zhiyun Ye, Shu-Yong Lin, Huiyong Yin, Hai-Long Piao, D Grahame Hardie, Sheng-Cai Lin
The major energy source for most cells is glucose, from which ATP is generated via glycolysis and/or oxidative metabolism. Glucose deprivation activates AMP-activated protein kinase (AMPK), but it is unclear whether this activation occurs solely via changes in AMP or ADP, the classical activators of AMPK. Here, we describe an AMP/ADP-independent mechanism that triggers AMPK activation by sensing the absence of fructose-1,6-bisphosphate (FBP), with AMPK being progressively activated as extracellular glucose and intracellular FBP decrease...
August 3, 2017: Nature
https://www.readbyqxmd.com/read/28704799/microrna-539-inhibits-glioma-cell-proliferation-and-invasion-by-targeting-dixdc1
#10
Junjie Quan, Jianqiang Qu, Le Zhou
Dysregulation of microRNAs (miRNAs) has been suggested to contribute to malignant progression of glioma. Previous studies have demonstrated that miR-539 is dysregulated in malignant progression of cancers. However, the potential role and mechanism of miR-539 in the progression of glioma remains unclear. In this study, we aimed to investigate the expression status and functional significance of miR-539 in glioma. We found that miR-539 expression was significantly decreased in glioma cell lines and tissues. Overexpression of miR-539 markedly inhibited glioma cell proliferation and invasion, while miR-539 suppression exhibited the opposite effect...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28678390/natural-product-withanolide-inspired-small-molecules-as-potent-inhibitors-of-wnt-signaling
#11
Herbert Waldmann, Michael Sheremet, Shobhna Kapoor, Peter Schröder, Kamal Kumar, Slava Ziegler
Wnt signaling is a fundamental pathway that drives embryonic development and is essential for stem cell maintenance and tissue homeostasis. Dysregulation of Wnt signaling is linked to various diseases and a constitutively active Wnt pathway drives tumorigenesis. Thus, disruption of the Wnt response is deemed a promising strategy for cancer drug discovery. However, only few clinical drug candidates that target Wnt signaling are available so far and new small molecules modulators of Wnt-related processes are in high demand...
July 5, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28659575/interaction-of-tankyrase-and-peroxiredoxin-ii-is-indispensable-for-the-survival-of-colorectal-cancer-cells
#12
Dong Hoon Kang, Doo Jae Lee, Sunmi Lee, So-Young Lee, Yukyung Jun, Yerin Kim, Youngeun Kim, Ju-Seog Lee, Dae-Kee Lee, Sanghyuk Lee, Eek-Hoon Jho, Dae-Yeul Yu, Sang Won Kang
Mammalian 2-Cys peroxiredoxin (Prx) enzymes are overexpressed in most cancer tissues, but their specific signaling role in cancer progression is poorly understood. Here we demonstrate that Prx type II (PrxII) plays a tumor-promoting role in colorectal cancer by interacting with a poly(ADP-ribose) polymerase (PARP) tankyrase. PrxII deletion in mice with inactivating mutation of adenomatous polyposis coli (APC) gene reduces intestinal adenomatous polyposis via Axin/β-catenin axis and thereby promotes survival...
June 28, 2017: Nature Communications
https://www.readbyqxmd.com/read/28628258/tankyrase-inhibition-regulates-corpus-luteum-development-and-luteal-function-in-gonadotropin-treated-rats
#13
Accialini Paula, Irusta Griselda, Bechis Andres, Bas Diana, Parborell Fernanda, Abramovich Dalhia, Tesone Marta
Tankyrases are physiological regulators of Axin, a protein involved in several cellular processes, including Wnt signaling. Here, we investigated the effect of a specific Tankyrase inhibitor (XAV939) in follicular-luteal dynamics, and its possible relationship with ovarian vascular development. Studies were designed to analyze the effect of intrabursa administration of XAV939 in gonadotropin-treated prepubertal rats. In particular, we examined follicle and corpus luteum development, steroidogenesis, angiogenic markers, and apoptotic parameters...
June 19, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/28624824/effect-of-tnf-%C3%AE-inhibition-on-bone-marrow-derived-mesenchymal-stem-cells-in-neurological-function-recovery-after-spinal-cord-injury-via-the-wnt-signaling-pathway-in-a-rat-model
#14
Ren-Jun Peng, Bing Jiang, Xi-Ping Ding, He Huang, Yi-Wei Liao, Gang Peng, Quan Cheng, Jian Xi
AIM: The present study aimed to examine the effect of tumor necrosis factor-α (TNF-α) inhibition on bone marrow-derived mesenchymal stem cells (BMSCs) in neurological function recovery after spinal cord injury (SCI) via the Wnt signaling pathway in a rat model. METHODS: The rat model of SCI was established using Allen's method. Seventy-two adult male Sprague Dawley (SD) rats were randomly assigned into 4 groups (18 rats in each group): the sham control group, saline control group, BMSCs group (injection with BMSCs at the injured site) and BMSCs + TNF-α group (injection with BMSCs under TNF-α treatment at the injured site)...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28619731/usp25-regulates-wnt-signaling-by-controlling-the-stability-of-tankyrases
#15
Daichao Xu, Jianping Liu, Tao Fu, Bing Shan, Lihui Qian, Lifeng Pan, Junying Yuan
Aberrant activation of the Wnt signaling pathway plays an important role in human cancer development. Wnt signaling is negatively regulated by Axin, a scaffolding protein that controls a rate-limiting step in the destruction of β-catenin, the central activator of the Wnt pathway. In Wnt-stimulated cells, Axin is rapidly modified by tankyrase-mediated poly(ADP-ribosyl)ation, which promotes the proteolysis of Axin and consequent stabilization of β-catenin. Thus, regulation of the levels and activity of tankyrases is mechanistically important in controlling Wnt signaling...
May 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28546513/the-siah-e3-ubiquitin-ligases-promote-wnt-%C3%AE-catenin-signaling-through-mediating-wnt-induced-axin-degradation
#16
Lei Ji, Bo Jiang, Xiaomo Jiang, Olga Charlat, Amy Chen, Craig Mickanin, Andreas Bauer, Wenqing Xu, Xiaoxue Yan, Feng Cong
The Wnt/β-catenin signaling pathway plays essential roles in embryonic development and adult tissue homeostasis. Axin is a concentration-limiting factor responsible for the formation of the β-catenin destruction complex. Wnt signaling itself promotes the degradation of Axin. However, the underlying molecular mechanism and biological relevance of this targeting of Axin have not been elucidated. Here, we identify SIAH1/2 (SIAH) as the E3 ligase mediating Wnt-induced Axin degradation. SIAH proteins promote the ubiquitination and proteasomal degradation of Axin through interacting with a VxP motif in the GSK3-binding domain of Axin, and this function of SIAH is counteracted by GSK3 binding to Axin...
May 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28546512/wnt5a-promotes-frizzled-4-signalosome-assembly-by-stabilizing-cysteine-rich-domain-dimerization
#17
Zachary J DeBruine, Jiyuan Ke, Kaleeckal G Harikumar, Xin Gu, Peter Borowsky, Bart O Williams, Wenqing Xu, Laurence J Miller, H Eric Xu, Karsten Melcher
Wnt/β-catenin signaling is activated when extracellular Wnt ligands bind Frizzled (FZD) receptors at the cell membrane. Wnts bind FZD cysteine-rich domains (CRDs) with high affinity through a palmitoylated N-terminal "thumb" and a disulfide-stabilized C-terminal "index finger," yet how these binding events trigger receptor activation and intracellular signaling remains unclear. Here we report the crystal structure of the Frizzled-4 (FZD4) CRD in complex with palmitoleic acid, which reveals a CRD tetramer consisting of two cross-braced CRD dimers...
May 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28532855/long-term-influence-of-prenatal-high-sucrose-intake-on-learning-and-memory-of-aged-rat-offspring-with-oxidative-stress-and-disruptions-in-nmdars-wnt-signaling-in-hippocampus
#18
Axin He, Yingying Zhang, Lingjun Li, Xueqin Feng, Bin Wei, Di Zhu, Yanping Liu, Lei Wu, Lubo Zhang, Zhice Xu, Miao Sun
Maternal over-nutrition may increase risks of various diseases in the offspring. Our recent work demonstrated that prenatal high sucrose (HS) could impair spatial acquisitionin the adolescentoffspringrats. This study investigated whether prenatal HS has a long-term impact on cognitive capabilities in the aged offspring rats. The aged HS offspring showed impaired glucose tolerance, significantly increased fasting insulin and insulin resistance index, with unchanged plasma glucose. In the navigation test, the aged HS offspring exhibited longer escape latency and longer swimming path length to the platform...
May 19, 2017: Brain Research
https://www.readbyqxmd.com/read/28515221/regulation-of-cerebral-arterial-bkca-channels-by-angiotensin-ii-signaling-in-adult-offspring-exposed-to-prenatal-high-sucrose-diets
#19
Xiuxia Gu, Axin He, Xiaorong Fan, Ruixiu Shi, Xueqin Feng, Le Bo, Lin Jiang, Na Li, Jue Wu, Yuxian Yang, Qinqin Gao, Zhice Xu
Prenatal insults have been shown to affect vascular functions, leading to increased risks of cardiovascular diseases in offspring. The present study determined whether high sucrose (HS) intake in pregnancy affected central vascular functions in middle cerebral artery (MCA) of offspring. Sprague-Dawley rats were fed a standard food and tap water with normal or high (20%) sucrose content during pregnancy. Offspring were maintained with normal diets and tap water. Central vascular functions and related ion channels were assessed in male offspring at 5 months old...
June 30, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28499884/inhibition-of-ubiquitin-specific-protease-34-usp34-induces-epithelial-mesenchymal-transition-and-promotes-stemness-in-mammary-epithelial-cells
#20
Eunhye Oh, Ji Young Kim, Daeil Sung, Youngkwan Cho, Nahyun Lee, Hyunsook An, Yoon-Jae Kim, Tae-Min Cho, Jae Hong Seo
Ubiquitin-specific protease 34 (USP34) is a deubiquitinating enzyme that regulates Axin stability and plays a critical role in Wnt/β-catenin signaling. We sought to investigate the role of USP34 on epithelial-mesenchymal (EMT) induction and its effects on mammary epithelial stem cells. USP34 expression levels were relatively lower in MDA-MB-231 and 4T1 mesenchymal-like cells when compared to epithelial-like cells. Inhibition of USP34 in NMuMG cells induced EMT, as evidenced by the upregulation of EMT markers including N-cadherin, phospho-Smad3, Snail and active-β-catenin, as well as the downregulation of Axin 1 and E-cadherin...
May 10, 2017: Cellular Signalling
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