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https://www.readbyqxmd.com/read/28644436/the-lats1-and-lats2-tumor-suppressors-beyond-the-hippo-pathway
#1
REVIEW
Noa Furth, Yael Aylon
Proper cellular functionality and homeostasis are maintained by the convergent integration of various signaling cascades, which enable cells to respond to internal and external changes. The Dbf2-related kinases LATS1 and LATS2 (LATS) have emerged as central regulators of cell fate, by modulating the functions of numerous oncogenic or tumor suppressive effectors, including the canonical Hippo effectors YAP/TAZ, the Aurora mitotic kinase family, estrogen signaling and the tumor suppressive transcription factor p53...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28642262/arterial-stiffness-induces-remodeling-phenotypes-in-pulmonary-artery-smooth-muscle-cells-via-yap-taz-mediated-repression-of-cyclooxygenase-2
#2
Paul B Dieffenbach, Christina Mallarino Haeger, Anna Maria F Coronata, Kyoung Moo Choi, Xaralabos Varelas, Daniel J Tschumperlin, Laura E Fredenburgh
Pulmonary arterial stiffness is an independent risk factor for mortality in pulmonary hypertension (PH), and plays a critical role in PH pathophysiology. We have recently demonstrated arterial stiffening early in experimental PH, along with evidence for a mechanobiologic feedback loop by which arterial stiffening promotes further cellular remodeling behaviors. Cyclooxygenase-2 (COX-2) and prostaglandin signaling have been implicated in stiffness-mediated regulation, with prostaglandin activity inversely correlated to matrix stiffness and remodeling behaviors in vitro, as well as to disease progression in rodent PH models...
June 22, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28634072/mitochondrial-dynamics-coordinate-cell-differentiation
#3
Masafumi Noguchi, Atsuko Kasahara
Cells differentiate into specific and functional lineages to build up tissues. It has been shown in several tissues that mitochondrial morphology, levels of "mitochondrial shaping" proteins, and mitochondrial functions change upon differentiation. In this review, we highlight the significance of mitochondrial dynamics and functions in tissue development, cell differentiation, and reprogramming processes. Signalling cascades are critical for tissue stem cell maintenance and cell fate determination, and growing evidence demonstrates mitochondria could act as a centre of intra and extracellular signals to coordinate signalling pathways, such as Notch, Wnt, and YAP/TAZ signalling...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28634071/the-novel-yap-target-gene-sgk1-upregulates-taz-activity-by-blocking-gsk3%C3%AE-mediated-taz-destabilization
#4
Geon Yoo, Tackhoon Kim, Chaeuk Chung, Deog-Su Hwang, Dae-Sik Lim
YAP (Yes-associated protein) and TAZ (transcription activator with PDZ binding motif) are important in tissue regeneration and cancer development, highlighting the importance of discovering partners that regulate their oncogenicity. SGK1 (serum/glucocorticoid regulated kinase 1), initially identified as a homolog of Akt in phosphoinositide 3-kinase signaling, acts as a serine/threonine protein kinase in multiple oncogenic pathways. However, possible links between SGK1 and Hippo-YAP/TAZ signaling remain unexplored...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28628115/stearoyl-coa-desaturase-1-regulates-lung-cancer-stemness-via-stabilization-and-nuclear-localization-of-yap-taz
#5
A Noto, C De Vitis, M E Pisanu, G Roscilli, G Ricci, A Catizone, G Sorrentino, G Chianese, O Taglialatela-Scafati, D Trisciuoglio, D Del Bufalo, M Di Martile, A Di Napoli, L Ruco, S Costantini, Z Jakopin, A Budillon, G Melino, G Del Sal, G Ciliberto, R Mancini
This corrects the article DOI: 10.1038/onc.2017.75.
June 19, 2017: Oncogene
https://www.readbyqxmd.com/read/28620202/nanotopological-plate-stimulates-osteogenic-differentiation-through-taz-activation
#6
Jun-Ha Hwang, Dong-Hyun Lee, Mi Ran Byun, A Rum Kim, Kyung Min Kim, Jung Il Park, Ho Taek Oh, Eun Sook Hwang, Kyu Back Lee, Jeong-Ho Hong
The topographical environment, which mimics the stem cell niche, provides mechanical cues to regulate the differentiation of mesenchymal stem cells (MSC). Diverse topographical variations have been engineered to investigate cellular responses; however, the types of mechanical parameters that affect cells, and their underlying mechanisms remain largely unknown. In this study, we screened nanotopological pillars with size gradient to activate transcriptional coactivator with PDZ binding motif (TAZ), which stimulates osteogenesis of MSC...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28616573/yap-and-the-hippo-pathway-in-pediatric-cancer
#7
REVIEW
Atif A Ahmed, Abdalla D Mohamed, Melissa Gener, Weijie Li, Eugenio Taboada
The Hippo pathway is an important signaling pathway that controls cell proliferation and apoptosis. It is evolutionarily conserved in mammals and is stimulated by cell-cell contact, inhibiting cell proliferation in response to increased cell density. During early embryonic development, the Hippo signaling pathway regulates organ development and size, and its functions result in the coordinated balance between proliferation, apoptosis, and differentiation. Its principal effectors, YAP and TAZ, regulate signaling by the embryonic stem cells and determine cell fate and histogenesis...
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28616323/the-emerging-role-of-yap-taz-in-mechanotransduction
#8
EDITORIAL
Zahra Mohri, Armando Del Rio Hernandez, Rob Krams
No abstract text is available yet for this article.
May 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28613007/transcriptional-coactivator-with-pdz-binding-motif-is-required-to-sustain-testicular-function-on-aging
#9
Mi Gyeong Jeong, Hyuna Song, Ji Hyun Shin, Hana Jeong, Hyo Kyeong Kim, Eun Sook Hwang
Transcriptional coactivator with PDZ-binding motif (TAZ) directly interacts with transcription factors and regulates their transcriptional activity. Extensive functional studies have shown that TAZ plays critical regulatory roles in stem cell proliferation, differentiation, and survival and also modulates the development of organs such as the lung, kidney, heart, and bone. Despite the importance of TAZ in stem cell maintenance, TAZ function has not yet been evaluated in spermatogenic stem cells of the male reproductive system...
June 14, 2017: Aging Cell
https://www.readbyqxmd.com/read/28604752/tumor-cell-derived-lactate-induces-taz-dependent-upregulation-of-pd-l1-through-gpr81-in-human-lung-cancer-cells
#10
J Feng, H Yang, Y Zhang, H Wei, Z Zhu, B Zhu, M Yang, W Cao, L Wang, Z Wu
The clinical success of immunotherapy that inhibits the negative immune regulatory pathway programmed cell death protein 1/PD-1 ligand (PD-1/PD-L1) has initiated a new era in the treatment of metastatic cancer. PD-L1 expression is upregulated in many solid tumors including lung cancer and functions predominantly in lactate-enriched tumor microenvironments. Here, we provided evidence for PD-L1 induction in response to lactate stimulation in lung cancer cells. Lactate-induced PD-L1 induction was mediated by its receptor GPR81...
June 12, 2017: Oncogene
https://www.readbyqxmd.com/read/28601008/fate-of-triazoles-in-softwood-upon-environmental-exposure
#11
Klara Kukowski, Veronika Martinská, Carl A Sedgeman, Paige Kuplic, Evguenii I Kozliak, Stephen Fisher, Alena Kubátová
Determining the fate of preservatives in commercial wood products is essential to minimize their losses and improve protective impregnation techniques. The fate of triazole fungicides in ponderosa pine wood was investigated in both outdoor and controlled-environment experiments using a representative triazole, tebuconazole (TAZ), which was accompanied by propiconazole (PAZ) in selected experiments. The study was designed to mimic industrial settings used in window frame manufacturing. To investigate the TAZ fate in detail, loosely and strongly bound fractions were differentiated using a multi-step extraction...
June 2, 2017: Chemosphere
https://www.readbyqxmd.com/read/28599430/transcriptional-co-activator-with-pdz-binding-motif-overexpression-promotes-cell-proliferation-and-transcriptional-co-activator-with-pdz-binding-motif-deficiency-induces-cell-cycle-arrest-in-neuroblastoma
#12
Liqun Yang, Mengying Huang, Juan Tan, Jianbing Hou, Jiang He, Feng Wang, Hongjuan Cui, Liang Yi
Transcriptional co-activator with PDZ-binding motif (TAZ) is a transcriptional co-activator which binds to a variety of transcription factors. An increasing number of studies have provided evidence that TAZ may be a positive regulator of cell proliferation and tumorigenesis. To reveal the underlying mechanisms by which TAZ controls these cellular processes, the present study used lentivirus expression system, flow cytometry, immunofluorescence and subcutaneous xenograft assays. The present study demonstrated that TAZ promoted and was indispensable for neuroblastoma cell proliferation and tumorigenesis...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28589555/common-and-distinctive-functions-of-the-hippo-effectors-taz-and-yap-in-skeletal-muscle-stem-cell-function
#13
Congshan Sun, Vanessa De Mello, Abdalla Mohamed, Huascar P Ortuste Quiroga, Amaya Garcia-Munoz, Abdullah Al Bloshi, Annie M Tremblay, Alexander von Kriegsheim, Elaina Collie-Duguid, Neil Vargesson, David Matallanas, Henning Wackerhage, Peter S Zammit
Hippo pathway downstream effectors Yap and Taz play key roles in cell proliferation and regeneration, regulating gene expression especially via Tead transcription factors. To investigate their role in skeletal muscle stem cells, we analysed Taz in vivo and ex vivo in comparison to Yap. siRNA knockdown or retroviral-mediated expression of wildtype human or constitutively active TAZ mutants in satellite cells showed that TAZ promoted proliferation, a function shared with YAP. However, at later stages of myogenesis, TAZ also enhanced myogenic differentiation of myoblasts, whereas YAP inhibits such differentiation...
June 7, 2017: Stem Cells
https://www.readbyqxmd.com/read/28581440/ubiquitin-ligase-rnf146-coordinates-bone-dynamics-and-energy-metabolism
#14
Yoshinori Matsumoto, Jose La Rose, Melissa Lim, Hibret A Adissu, Napoleon Law, Xiaohong Mao, Feng Cong, Paula Mera, Gerard Karsenty, David Goltzman, Adele Changoor, Lucia Zhang, Megan Stajkowski, Marc D Grynpas, Carsten Bergmann, Robert Rottapel
Cleidocranial dysplasia (CCD) is an autosomal dominant human disorder characterized by abnormal bone development that is mainly due to defective intramembranous bone formation by osteoblasts. Here, we describe a mouse strain lacking the E3 ubiquitin ligase RNF146 that shows phenotypic similarities to CCD. Loss of RNF146 stabilized its substrate AXIN1, leading to impairment of WNT3a-induced β-catenin activation and reduced Fgf18 expression in osteoblasts. We show that FGF18 induces transcriptional coactivator with PDZ-binding motif (TAZ) expression, which is required for osteoblast proliferation and differentiation through transcriptional enhancer associate domain (TEAD) and runt-related transcription factor 2 (RUNX2) transcription factors, respectively...
June 5, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28581256/taz-is-involved-in-transcriptional-complexes-regulating-smooth-muscle-cell-differentiation
#15
Eyal Bengal
TGFβ signaling plays an important role in the differentiation of vascular smooth muscle cells (VSMCs), yet the mechanism remains largely unknown. The study by Pagiatakis et al. identifies the transcriptional coactivator TAZ as a mediator of TGFβ signaling in VSMC-specific transcription. TAZ is involved in the formation of stable ternary complexes of SRF/Myocardin on CArG elements that are required for the transcription of VSMC structural genes.
June 2017: FEBS Journal
https://www.readbyqxmd.com/read/28579171/the-ndr-lats-protein-kinases-in-immunology-and-cancer-biology
#16
REVIEW
Ahmad A D Sharif, Alexander Hergovich
The NDR (nuclear Dbf2-related)/LATS (large tumour suppressor) family of kinases represents a subclass of the AGC (protein kinase A (PKA)/PKG/PKC-like) group of serine/threonine protein kinases. Members of the NDR/LATS family are vital components of conserved pathways controlling essential cellular processes, such as proliferation (cell cycle progression) and cell death. In particular, the central involvement of NDR/LATS as YAP/TAZ kinases in the Hippo tissue growth control pathway has gained much interest. In this review, we summarize the roles of mammalian NDR1/2 (aka STK38/STK38L) and LATS1/2 in immunity and cancer biology...
June 1, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28570566/targeting-yap-taz-tead-protein-protein-interactions-using-fragment-based-and-computational-modeling-approaches
#17
Hung Yi Kristal Kaan, Adelene Y L Sim, Siew Kim Joyce Tan, Chandra Verma, Haiwei Song
The Hippo signaling pathway, which is implicated in the regulation of organ size, has emerged as a potential target for the development of cancer therapeutics. YAP, TAZ (transcription co-activators) and TEAD (transcription factor) are the downstream transcriptional machinery and effectors of the pathway. Formation of the YAP/TAZ-TEAD complex leads to transcription of growth-promoting genes. Conversely, disrupting the interactions of the complex decreases cell proliferation. Herein, we screened a 1000-member fragment library using Thermal Shift Assay and identified a hit fragment...
2017: PloS One
https://www.readbyqxmd.com/read/28554198/role-of-taz-in-lysophosphatidic-acid-induced-migration-and-proliferation-of-human-adipose-derived-mesenchymal-stem-cells
#18
Won Min Mo, Yang Woo Kwon, Il Ho Jang, Eun Jung Choi, Sang Mo Kwon, Jae Ho Kim
Transcriptional co-activator with a PDZ-binding motif (TAZ) is an important factor in lysophosphatidic acid (LPA)-induced promotion of migration and proliferation of human mesenchymal stem cells (MSCs). The expression of TAZ significantly increased at 6 h after LPA treatment, and TAZ knockdown inhibited the LPA-induced migration and proliferation of MSCs. In addition, embryonic fibroblasts from TAZ knockout mice exhibited the reduction in LPA-induced migration and proliferation. The LPA1 receptor inhibitor Ki16425 blocked LPA responses in MSCs...
May 30, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28552397/morin-attenuates-diethylnitrosamine-induced-rat-liver-fibrosis-and-hepatic-stellate-cell-activation-by-co-ordinated-regulation-of-hippo-yap-and-tgf-%C3%AE-1-smad-signaling
#19
Perumal NaveenKumar, Perumal MadanKumar, Halagowder Devaraj, Sivasithamparam NiranjaliDevaraj
Despite great progress in understanding the activation of hepatic stellate cells (HSCs) during liver fibrosis, therapeutic approaches to inhibit HSC activation remain very limited. Recent reports highlight Yes-associated protein (Yap) and transforming growth factor-β1 (TGF-β1) as critical regulators of HSC activation and henceforth a compound targeting Hippo/Yap and TGF-β1/Smad pathways would be a potential anti-fibrotic candidate. Morin, a dietary flavonoid, was earlier reported to inhibit HSC proliferation and induction of apoptosis of cultured HSCs, mainly by suppressing Wnt/β-catenin and NF-κB signaling, but its effect on Hippo/Yap and TGF-β1/Smad pathways was not determined...
May 25, 2017: Biochimie
https://www.readbyqxmd.com/read/28534974/taz-overexpression-is-associated-with-epithelial-mesenchymal-transition-in-cisplatin-resistant-gastric-cancer-cells
#20
Liang Ge, Dong-Song Li, Fei Chen, Ji-Dong Feng, Bai Li, Tie-Jun Wang
Gastric cancer is one of the common malignant diseases. The poor treatment outcome is mainly due to chemotherapeutic resistance. Therefore, it is important to determine the molecular mechanism of drug resistance in gastric cancer. To explore the mechanisms of cisplatin resistance in gastric cancer cells, several approaches were performed including MTT assay, real-time RT-PCR, western blot analysis, migration and invasion assays, wound healing assay, and transfection. We found that cisplatin-resistant (CR) gastric cancer cells acquired epithelial-mesenchymal transition (EMT) phenotype...
May 16, 2017: International Journal of Oncology
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