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Chengjie Lin, Guandou Yuan, Zhigao Hu, Yonglian Zeng, Xiaoqiang Qiu, Hongping Yu, Songqing He
The present study aimed to investigate the regulatory networks involving long noncoding RNA (lncRNA), microRNA (miRNA), mRNA, genetic mutations and epigenetic modifications in hepatocellular carcinoma (HCC) by analyzing datasets from The Cancer Genome Atlas (TCGA) database. TCGA was mined, and miRNAs, lncRNAs and mRNAs that were differentially expressed in HCC were identified using R software. A gene regulatory network was constructed using Cytoscape software. Representative genes were selected for functional enrichment analysis using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes...
December 5, 2018: Molecular Medicine Reports
Lina Lv, Baihua Chen, Jun Liu, Jing Chen, Chao Xu, Yanqiu Yang
Complexation of U(vi) with pyridazine-3-carboxylate (PDZ) and pyrazine-2-carboxylate (PAZ) was studied by spectrophotometry, potentiometry and microcalorimetry in 1.0 mol dm-3 NaClO4. Three complexes, [UO2L]+, UO2L2(aq) and [UO2L3]-, were identified and their stability constants (log β) and the corresponding formation enthalpies were determined. The thermodynamic parameters indicate that the formation of the three complexes is endothermic and driven exclusively by entropy. 1H and 13C-NMR data provide insight into the coordination modes of the complexes which corroborate with the thermodynamic data...
December 10, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
Remco A Mentink, Lorenzo Rella, Tomasz W Radaszkiewicz, Tomáš Gybel, Marco C Betist, Vitězslav Bryja, Hendrik C Korswagen
Van Gogh-like (Vangl) and Prickle (Pk) are core components of the non-canonical Wnt planar cell polarity pathway that controls epithelial polarity and cell migration. Studies in vertebrate model systems have suggested that Vangl and Pk may also inhibit signaling through the canonical Wnt/β-catenin pathway, but the functional significance of this potential cross-talk is unclear. In the nematode C. elegans, the Q neuroblasts and their descendants migrate in opposite directions along the anteroposterior body axis...
December 7, 2018: PLoS Genetics
Wei-Wei Pan, Toshiro Moroishi, Ja Hyun Koo, Kun-Liang Guan
The Hippo pathway controls organ size and tissue homeostasis, and its dysregulation often contributes to tumorigenesis. Extensive studies have shown that the Hippo pathway inhibits cell proliferation, and survival in a cell-autonomous manner. We examined the function of the Hippo pathway kinases LATS1/2 (large tumor suppressor 1 and 2) in cancer cells. As expected, loss of LATS1/2 promotes cancer cell growth in most cell lines. Surprisingly, however, LATS1/2 deletion inhibits the growth of murine MC38 colon cancer cells, especially under detachment conditions...
December 10, 2018: Oncogene
Na Wang, Peng Xue, Ziyi Li, Yukun Li
Whether insulin receptor substrate 1 (IRS-1) inhibits or promotes the osteogenic proliferation and differentiation in vitro remains controversial. Transcriptional co-activator with PDZ-binding motif (TAZ) plays a vital role in the osteogenesis of bone marrow mesenchymal stem cells (BMSCs), and strongly activates the expression of the osteogenic differentiation markers. In this study, we found that IRS-1 and TAZ followed similar increasing expression patterns at the early stage of osteogenic differentiation...
December 7, 2018: Biology Open
Fei Ye, Yuxin Huang, Jianchao Li, Yuqian Ma, Chensu Xie, Zexu Liu, Xiaoying Deng, Jun Wan, Tian Xue, Wei Liu, Mingjie Zhang
INAD assembles key enzymes of Drosophila compound eye photo-transduction pathway into a supramolecular complex, supporting efficient and fast light signaling. However, the molecular mechanism governing the interaction between INAD and NORPA (phospholipase Cβ, PLCβ), a key step for the fast kinetics of the light signaling, is not known. Here, we show that the NORPA C-terminal coiled-coil domain and PDZ-binding motif (CC-PBM) synergistically bind to INAD PDZ45 tandem with an unexpected mode and unprecedentedly high affinity...
December 10, 2018: ELife
Nao Komatsu, Mikihito Kajiya, Souta Motoike, Manabu Takewaki, Susumu Horikoshi, Tomoyuki Iwata, Kazuhisa Ouhara, Katsuhiro Takeda, Shinji Matsuda, Tsuyoshi Fujita, Hidemi Kurihara
BACKGROUND: Three-dimensional (3D) floating culture clumps of mesenchymal stem cell (MSC)/extracellular matrix (ECM) complexes (C-MSCs) consist of cells and self-produced ECM. Previous studies have demonstrated that C-MSCs can be transplanted into bony lesions without an artificial scaffold to induce bone regeneration. Moreover, osteoinductive medium (OIM)-treated C-MSCs (OIM-C-MSCs) have shown rapid and increased new bone formation in vivo. To apply OIM-C-MSCs for novel bone regenerative cell therapy, their cellular properties at the molecular level must be elucidated...
December 7, 2018: Stem Cell Research & Therapy
Sahar S Bhat, Roshia Ali, Firdous A Khanday
Syntrophins are a family of 59 kDa peripheral membrane-associated adapter proteins, containing multiple protein-protein and protein-lipid interaction domains. The syntrophin family consists of five isoforms that exhibit specific tissue distribution, distinct sub-cellular localization and unique expression patterns implying their diverse functional roles. These syntrophin isoforms form multiple functional protein complexes and ensure proper localization of signalling proteins and their binding partners to specific membrane domains and provide appropriate spatiotemporal regulation of signalling pathways...
December 4, 2018: Cell Proliferation
Diana M Elizondo, Temesgen E Andargie, Naomi L Haddock, Ricardo L Louzada da Silva, Tatiana Rodrigues de Moura, Michael W Lipscomb
Allograft Inflammatory Factor-1 (AIF1) is a cytoplasmic scaffold protein that contains Ca2+ binding EF-hand and PDZ interaction domains important for mediating intracellular signaling complexes in immune cells. The protein plays a dominant role in both macrophage- and dendritic cell (DC)-mediated inflammatory responses. This study now reports that AIF1 expression in DC is important in directing CD8+ T cell effector responses. Silencing AIF1 expression in murine CD11c+ DC suppressed antigen-specific CD8+ T cell activation, marked by reduced CXCR3, IFNγ and Granzyme B expression, and restrained proliferation...
December 4, 2018: Journal of Leukocyte Biology
Arvind Kumar Gupta, Debashree Behera, Balasubramanian Gopal
The crystal structure of Mycobacterium tuberculosis high-temperature requirement A (HtrA) protein was determined at 1.83 Å resolution. This membrane-associated protease is essential for the survival of M. tuberculosis. The crystal structure reveals that interactions between the PDZ domain and the catalytic domain in HtrA lead to an inactive conformation. This finding is consistent with its proposed role as a regulatory protease that is conditionally activated upon appropriate environmental triggers. The structure provides a basis for directed studies to evaluate the role of this essential protein and the regulatory pathways that are influenced by this protease...
December 1, 2018: Acta Crystallographica. Section F, Structural Biology Communications
Sun-Hong Hwang, Sunhoe Bang, Kyung Shin Kang, Deborah Kang, Jongkyeong Chung
Wnt signaling pathway plays critical roles in body axes patterning, cell fate specification, cell proliferation, cell migration, stem cell maintenance, cancer development and etc. Deregulation of this pathway can be causative of cancer, metabolic disease and neurodegenerative disease such as Parkinson`s disease. Among the core components of Wnt signaling pathway, we discovered that Dishevelled (Dsh) interacts with ULK1 and is phosphorylated by ULK1. Unexpectedly, the knockdown of ULK1 elicited a marked increase in Wnt/β-catenin signaling...
November 27, 2018: Biochemical and Biophysical Research Communications
Aman Patel, Junling Zhao, Yongping Yue, Keqing Zhang, Dongsheng Duan, Yi Lai
BACKGROUND: Loss of sarcolemmal nNOSμ is a common manifestation in a wide variety of muscle diseases and contributes to the dysregulation of multiple muscle activities. Given the critical role sarcolemmal nNOSμ plays in muscle, restoration of sarcolemmal nNOSμ should be considered as an important therapeutic goal. METHODS: nNOSμ is anchored to the sarcolemma by dystrophin spectrin-like repeats 16 and 17 (R16/17) and the syntrophin PDZ domain (Syn PDZ). To develop a strategy that can independently restore sarcolemmal nNOSμ, we engineered an R16/17-Syn PDZ fusion construct and tested whether this construct alone is sufficient to anchor nNOSμ to the sarcolemma in three different mouse models of Duchenne muscular dystrophy (DMD)...
November 22, 2018: Skeletal Muscle
Yongshun Wang, Wei Cao, Jinjin Cui, Yang Yu, Yubo Zhao, Jian Shi, Jian Wu, Zhengyuan Xia, Bo Yu, Jingjin Liu
BACKGROUND/AIMS: Increasing wall stress or biomechanical stretch experienced by arteries influences the initiation of atherosclerotic lesions. This initiation is mediated by Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), which are both effectors of the Hippo pathway. In this study, the functional roles of YAP/TAZ proteins in the regulation of the stretch-mediated programing of human umbilical arterial smooth muscle cells (HUASMCs) to a proliferative phenotype were examined...
2018: Cellular Physiology and Biochemistry
Satoshi Noguchi, Akira Saito, Takahide Nagase
Tissue fibrosis is a pathological condition that is associated with impaired epithelial repair and excessive deposition of extracellular matrix (ECM). Fibrotic lesions increase the risk of cancer in various tissues, but the mechanism linking fibrosis and cancer is unclear. Yes-associated protein (YAP) and the transcriptional coactivator with PDZ-binding motif (TAZ) are core components of the Hippo pathway, which have multiple biological functions in the development, homeostasis, and regeneration of tissues and organs...
November 20, 2018: International Journal of Molecular Sciences
Banavathy S Kruthika, Ruchi Jain, A Arivazhagan, R D Bharath, T C Yasha, Paturu Kondaiah, Vani Santosh
PURPOSE: Peritumoural brain zone (PT) of glioblastoma (GBM) is the area where tumour recurrence is often observed. We aimed to identify differentially regulated genes between tumour core (TC) and PT to understand the underlying molecular characteristics of infiltrating tumour cells in PT. METHODS: 17 each histologically characterised TC and PT tissues of GBM along with eight control tissues were subjected to cDNA Microarray. PT tissues contained 25-30% infiltrating tumour cells...
November 20, 2018: Journal of Neuro-oncology
Xinyan Ji, Lihua Song, Li Sheng, Anhui Gao, Yang Zhao, Shixun Han, Yuchao Zhang, Chu Zhu, Simeng Zhao, Zhe Wang, Bohan Xu, Li Li, Jia Li, Ninghua Tan, Bin Zhao
The Hippo pathway restricts organ size during development and its inactivation plays a crucial role in cancer. Yes-associated protein (YAP) and its paralog transcriptional coactivator with PSD-95/Dlg/ZO-1 (PDZ)-binding motif (TAZ) are transcription co-activators and effectors of the Hippo pathway mediating aberrant enlargement of organs and tumor growth upon Hippo pathway inactivation. It has been demonstrated that genetic inactivation of YAP could be an effective approach to inhibit tumorigenesis. In order to identify pharmacological inhibitors of YAP, we screened a library of 52,683 compounds using a YAP-specific reporter assay...
November 16, 2018: Cancers
Shweta Sharma, Rishov Goswami, David X Zhang, Shaik O Rahaman
Substrate stiffness (or rigidity) of the extracellular matrix has important functions in numerous pathophysiological processes including fibrosis. Emerging data support a role for both a mechanical signal, for example, matrix stiffness, and a biochemical signal, for example, transforming growth factor β1 (TGFβ1), in epithelial-mesenchymal transition (EMT), a process critically involved in fibrosis. Here, we report evidence showing that transient receptor potential vanilloid 4 (TRPV4), a mechanosensitive channel, is the likely mediator of EMT in response to both TGFβ1 and matrix stiffness...
November 18, 2018: Journal of Cellular and Molecular Medicine
Rodolfo Daniel Cervantes-Villagrana, Sendi Rafael Adame-García, Irving García-Jimenez, Víctor Manuel Color-Aparicio, Yarely Mabell Beltran-Navarro, Gabriele M König, Evi Kostenis, Guadalupe Reyes-Cruz, J Silvio Gutkind, José Vázquez-Prado
G protein-coupled receptors stimulate Rho guanine nucleotide exchange factors that promote mammalian cell migration. Rac and Rho GTPases exert opposing effects on cell morphology, and are stimulated downstream of Gβγ and Gα12/13 or Gαq , respectively. These Gα subunits might in turn favor Rho pathways by preventing Gβγ signaling to Rac. Here, we investigated whether Gβγ signaling to phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 1 (P-REX1), a key Gβγ chemotactic effector, is directly controlled by Rho-activating Gα subunits...
November 16, 2018: Journal of Biological Chemistry
Christie K Campla, Hannah Mast, Lijin Dong, Jingqi Lei, Stephanie Halford, Sumathi Sekaran, Anand Swaroop
Regulation of cell type-specific gene expression is critical for generating neuronal diversity. Transcriptome analyses have unraveled extensive heterogeneity of transcribed sequences in retinal photoreceptors because of alternate splicing and/or promoter usage. Here we show that Frmpd1 (FERM and PDZ domain containing 1) is transcribed from an alternative promoter specifically in the retina. Electroporation of Frmpd1 promoter region, -505 to +382 bp, activated reporter gene expression in mouse retina in vivo...
November 15, 2018: Human Molecular Genetics
Chao-Ying Deng, Huan Zhang, Yao Wu, Li-Li Ding, Yue Pan, Shu-Tao Sun, Ya-Jun Li, Li Wang, Wei Qian
In bacterial cells, histidine kinases (HKs) are receptors that monitor environmental and intracellular stimuli. HKs and their cognate response regulators constitute two-component signalling systems (TCSs) that modulate cellular homeostasis through reversible protein phosphorylation. Here the authors show that the plant pathogen Xanthomonas campestris pv. campestris responds to osmostress conditions by regulating the activity of a HK (VgrS) via irreversible, proteolytic modification. This regulation is mediated by a periplasmic, PDZ-domain-containing protease (Prc) that cleaves the N-terminal sensor region of VgrS...
November 15, 2018: Nature Communications
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