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https://www.readbyqxmd.com/read/28327630/rassf-proteins-as-modulators-of-mst1-kinase-activity
#1
Aruna Bitra, Srinivas Sistla, Jessy Mariam, Harshada Malvi, Ruchi Anand
Rassf1A/5 tumor suppressors serve as adaptor proteins possessing a modular architecture with the C-terminal consisting of a coiled-coil SARAH (Salvador-Rassf-Hippo) domain and the central portion being composed of Ras associated (RA) domain. Here, we investigate the effect of Rassf effectors on Mst1 function by mapping the interaction of various domains of Rassf1A/5 and Mst1 kinase using surface plasmon resonance (SPR). The results revealed that apart from the C-terminal SARAH domain of Mst1 which interacts to form heterodimers with Rassf1A/5, the N-terminal kinase domain of Mst1 plays a crucial role in the stabilization of this complex...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28323616/yap-is-essential-for-mechanical-force-production-and-epithelial-cell-proliferation-during-lung-branching-morphogenesis
#2
Chuwen Lin, Erica Yao, Kuan Zhang, Xuan Jiang, Stacey Croll, Katherine Thompson-Peer, Pao-Tien Chuang
Branching morphogenesis is a fundamental program for tissue patterning. We show that active YAP, a key mediator of Hippo signaling, is distributed throughout the murine lung epithelium and loss of epithelial YAP severely disrupts branching. Failure to branch is restricted to regions where YAP activity is removed. This suggests that YAP controls local epithelial cell properties. In support of this model, mechanical force production is compromised and cell proliferation is reduced in Yap mutant lungs. We propose that defective force generation and insufficient epithelial cell number underlie the branching defects...
March 21, 2017: ELife
https://www.readbyqxmd.com/read/28315837/a-search-for-genes-mediating-the-growth-promoting-function-of-tgf%C3%AE-in-the-drosophila-melanogaster-wing-disc
#3
Covadonga F Hevia, Ana López-Varea, Nuria Esteban, Jose F de Celis
TGFβ signalling has a complex influence in cell proliferation, acting to stop cell division in differentiating cells, but also promoting cell division in immature cells. The activity of the pathway in Drosophila is mostly required to stimulate the proliferation of neural and epithelial tissues. Most interestingly, this function is not absolutely required for cell division, but it is needed for these tissues to reach their correct size. It is not known how TGFβ signalling promotes cell division in imaginal discs, or what are the interactions between TGFβ activity and other signalling pathways regulating cell proliferation...
March 17, 2017: Genetics
https://www.readbyqxmd.com/read/28315521/systematic-morphological-profiling-of-human-gene-and-allele-function-via-cell-painting
#4
Mohammad Hossein Rohban, Shantanu Singh, Xiaoyun Wu, Julia B Berthet, Mark-Anthony Bray, Yashaswi Shrestha, Xaralabos Varelas, Jesse S Boehm, Anne E Carpenter
We hypothesized that human genes and disease-associated alleles might be systematically functionally annotated using morphological profiling of cDNA constructs, via a microscopy-based Cell Painting assay. Indeed, 50% of the 220 tested genes yielded detectable morphological profiles, which grouped into biologically meaningful gene clusters consistent with known functional annotation (e.g., the RAS-RAF-MEK-ERK cascade). We used novel subpopulation-based visualization methods to interpret the morphological changes for specific clusters...
March 18, 2017: ELife
https://www.readbyqxmd.com/read/28299672/roles-of-runx-in-hippo-pathway-signaling
#5
Antonino Passaniti, Jessica L Brusgard, Yiting Qiao, Marius Sudol, Megan Finch-Edmondson
The Runt-domain (RD) transcription factors (RUNX genes) are an important family of transcriptional mediators that interact with a variety of proteins including the Hippo pathway effector proteins, YAP and TAZ. In this chapter we focus on two examples of RUNX-TAZ/YAP interactions that have particular significance in human cancer. Specifically, recent evidence has found that RUNX2 cooperates with TAZ to promote epithelial to mesenchymal transition mediated by the soluble N-terminal ectodomain of E-Cadherin, sE-Cad...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28293931/investigation-of-the-possible-role-of-the-hippo-yap1-pathway-in-asthma-and-allergy
#6
Lili E Fodor, András Gézsi, Ldikó Ungvári, Agnes F Semsei, Zsófia Gál, Adrienne Nagy, Gabriella Gálffy, Lilla Tamási, András Kiss, Péter Antal, Csaba Szalai
PURPOSE: Several lines of evidence indicate that the Hippo/Yes-associated protein 1 (YAP1) pathways might play a role in the pathogenesis of asthma. To investigate the possible role of the Hippo/YAP1 pathway in the pathogenesis of asthma or its phenotypes. METHODS: The levels of gene expressions of the members of the Hippo/YAP1 were compared. The presence of the proteins of the YAP1 and FRMD6 were analyzed with Western blot in induced sputum of 18 asthmatic subjects and 10 control subjects...
May 2017: Allergy, Asthma & Immunology Research
https://www.readbyqxmd.com/read/28292426/kibra-and-merlin-activate-the-hippo-pathway-spatially-distinct-from-and-independent-of-expanded
#7
Ting Su, Michael Z Ludwig, Jiajie Xu, Richard G Fehon
The Hippo pathway is emerging as a key evolutionarily conserved signaling mechanism that controls organ size. Three membrane-associated proteins, Kibra, Merlin, and Expanded, regulate pathway activity, but the precise molecular mechanism by which they function is still poorly understood. Here we provide evidence that Merlin and Kibra activate Hippo signaling in parallel to Expanded at a spatially distinct cellular domain, the medial apical cortex. Merlin and Kibra together recruit the adapter protein Salvador, which in turn recruits the core kinase Hippo...
March 13, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28289060/the-crumbs3-polarity-protein
#8
Ben Margolis
The Crumbs proteins are evolutionarily conserved apical transmembrane proteins. Drosophila Crumbs was discovered via its crucial role in epithelial polarity during fly embryogenesis. Crumbs proteins have variable extracellular domains but a highly conserved intracellular domain that can bind FERM and PDZ domain proteins. Mammals have three Crumbs genes and this review focuses on Crumbs3, the major Crumbs isoform expressed in mammalian epithelial cells. Although initial work has highlighted the role of Crumbs3 in polarity, more recent studies have found it has an important role in tissue morphogenesis functioning as a linker between the apical membrane and the actin cytoskeleton...
March 13, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28281933/spatial-regulation-of-araf-controls-the-mst2-hippo-pathway
#9
Jens Rauch, Walter Kolch
The RAF-MAPK signaling pathway regulates several very diverse cellular processes such as proliferation, differentiation, apoptosis, and transformation. While the canonical function of RAF kinases within the MAPK pathway is the activation of MEK, our group could demonstrate an important crosstalk between RAF signaling and the pro-apoptotic mammalian sterile 20-like kinase (MST2) tumor suppressor pathway in several cancer entities, including head and neck, colon, and breast. Here, the RAF kinases CRAF and ARAF sequester and inhibit the pro-apoptotic kinase MST2 independently of their own kinase activity...
March 10, 2017: Small GTPases
https://www.readbyqxmd.com/read/28280861/a-growing-role-for-the-hippo-signaling-pathway-in-the-heart
#10
REVIEW
Yu Zhang, Dominic P Del Re
Heart disease is a major cause of clinical morbidity and mortality, and a significant health and economic burden worldwide. The loss of functional cardiomyocytes, often a result of myocardial infarction, leads to impaired cardiac output and ultimately heart failure. Therefore, efforts to improve cardiomyocyte viability and stimulate cardiomyocyte proliferation remain attractive therapeutic goals. Originally identified in Drosophila, the Hippo signaling pathway is highly conserved from flies to humans and regulates organ size through modulation of both cell survival and proliferation...
March 10, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28279717/yap-and-wwtr1-new-targets-for-skin-cancer-treatment
#11
Thomas Andl, Linli Zhou, Kun Yang, Ana Luisa Kadekaro, Yuhang Zhang
The core components of the Hippo signaling pathway are a cascade of kinases that govern the phosphorylation of downstream transcriptional co-activators, namely, YES-associated protein (YAP) and WW domain-containing transcription regulator protein 1 (WWTR1, also known as TAZ). The Hippo signaling pathway is considered an important tumor-suppressor pathway, and its dysregulation has been noted in a variety of human cancers, in which YAP/WWTR1 enable cancerous cells to overcome contact inhibition, and to grow and spread uncontrollably...
March 6, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28274274/a-novel-form-of-necrosis-triad-occurs-in-human-huntington-s-disease
#12
Emiko Yamanishi, Kazuko Hasegawa, Kyota Fujita, Shizuko Ichinose, Saburo Yagishita, Miho Murata, Kazuhiko Tagawa, Takumi Akashi, Yoshinobu Eishi, Hitoshi Okazawa
We previously reported transcriptional repression-induced atypical cell death of neuron (TRIAD), a new type of necrosis that is mainly regulated by Hippo pathway signaling and distinct from necroptosis regulated by RIP1/3 pathway. Here, we examined the ultrastructural and biochemical features of neuronal cell death in the brains of human HD patients in parallel with the similar analyses using mutant Htt-knock-in (Htt-KI) mice. LATS1 kinase, the critical regulator and marker of TRIAD, is actually activated in cortical neurons of postmortem human HD and of Htt-KI mouse brains, while apoptosis promoter kinase Plk1 was inactivated in human HD brains...
March 8, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28273460/agrin-as-a-mechanotransduction-signal-regulating-yap-through-the-hippo-pathway
#13
Sayan Chakraborty, Kizito Njah, Ajaybabu V Pobbati, Ying Bena Lim, Anandhkumar Raju, Manikandan Lakshmanan, Vinay Tergaonkar, Chwee Teck Lim, Wanjin Hong
The Hippo pathway effectors YAP and TAZ act as nuclear sensors of mechanical signals in response to extracellular matrix (ECM) cues. However, the identity and nature of regulators in the ECM and the precise pathways relaying mechanoresponsive signals into intracellular sensors remain unclear. Here, we uncover a functional link between the ECM proteoglycan Agrin and the transcriptional co-activator YAP. Importantly, Agrin transduces matrix and cellular rigidity signals that enhance stability and mechanoactivity of YAP through the integrin-focal adhesion- and Lrp4/MuSK receptor-mediated signaling pathways...
March 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28270513/a-shortcut-for-early-macrophage-recruitment-into-tumors-by-activated-oncogenes
#14
REVIEW
Liv Austenaa, Gioacchino Natoli
Macrophages play an important role in tumor promotion, usually acting as facilitators of cancer initiation and progression. However, it is not clear how macrophages impact early phases of tumorigenesis. Using genetically modified mouse models, Guo et al. (pp. 247-259) demonstrated that tumor-initiating cells with an activated Hippo pathway are able to recruit macrophages starting from the very early phases of cancer development, mainly through direct activation of genes encoding macrophage chemoattractants and survival factors...
February 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28266532/a-potential-large-and-persistent-black-carbon-forcing-over-northern-pacific-inferred-from-satellite-observations
#15
Zhongshu Li, Junfeng Liu, Denise L Mauzerall, Xiaoyuan Li, Songmiao Fan, Larry W Horowitz, Cenlin He, Kan Yi, Shu Tao
Black carbon (BC) aerosol strongly absorbs solar radiation, which warms climate. However, accurate estimation of BC's climate effect is limited by the uncertainties of its spatiotemporal distribution, especially over remote oceanic areas. The HIAPER Pole-to-Pole Observation (HIPPO) program from 2009 to 2011 intercepted multiple snapshots of BC profiles over Pacific in various seasons, and revealed a 2 to 5 times overestimate of BC by current global models. In this study, we compared the measurements from aircraft campaigns and satellites, and found a robust association between BC concentrations and satellite-retrieved CO, tropospheric NO2, and aerosol optical depth (AOD) (R(2) > 0...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28265104/mir-285-yki-mask-double-negative-feedback-loop-mediates-blood-brain-barrier-integrity-in-drosophila
#16
Dong Li, Yanling Liu, Chunli Pei, Peng Zhang, Linqing Pan, Jing Xiao, Songshu Meng, Zengqiang Yuan, Xiaolin Bi
The Hippo signaling pathway is highly conserved from Drosophila to mammals and plays a central role in maintaining organ size and tissue homeostasis. The blood-brain barrier (BBB) physiologically isolates the brain from circulating blood or the hemolymph system, and its integrity is strictly maintained to perform sophisticated neuronal functions. Until now, the underlying mechanisms of subperineurial glia (SPG) growth and BBB maintenance during development are not clear. Here, we report an miR-285-Yorkie (Yki)/Multiple Ankyrin repeats Single KH domain (Mask) double-negative feedback loop that regulates SPG growth and BBB integrity...
March 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28260491/control-of-myofibroblast-differentiation-and-function-by-cytoskeletal-signaling
#17
REVIEW
N Sandbo, L V Smolyaninova, S N Orlov, N O Dulin
The cytoskeleton consists of three distinct types of protein polymer structures - microfilaments, intermediate filaments, and microtubules; each serves distinct roles in controlling cell shape, division, contraction, migration, and other processes. In addition to mechanical functions, the cytoskeleton accepts signals from outside the cell and triggers additional signals to extracellular matrix, thus playing a key role in signal transduction from extracellular stimuli through dynamic recruitment of diverse intermediates of the intracellular signaling machinery...
December 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28259973/furin-promotes-epithelial-mesenchymal-transition-in-pancreatic-cancer-cells-via-hippo-yap-pathway
#18
Youli Zhang, Meng Zhou, Hong Wei, Hailang Zhou, Junbo He, Ying Lu, Dawei Wang, Baoding Chen, Jian Zeng, Wanxin Peng, Fengyi Du, Aihua Gong, Min Xu
Furin, a well-characterized proprotein convertase, plays an important role in many diseases and links to tumor metastasis. However, the role of furin in pancreatic cancer progression remains to be elucidated. In the present study, we found that furin promotes the growth and the epithelial-mesenchymal transition (EMT) of pancreatic cancer cells. First, we found that furin knockdown significantly inhibited proliferation, invasion and migration in BxPC3 and SW1990 cells, while furin overexpression promoted the above behavior in PANC1 and PaTu8988 cells...
March 2, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28257933/genetic-ablation-of-the-mammalian-sterile-20-like-kinase-1-mst1-improves-cell-reprogramming-efficiency-and-increases-induced-pluripotent-stem-cell-proliferation-and-survival
#19
Abigail Robertson, Tamer M A Mohamed, Zeinab El Maadawi, Nicholas Stafford, Thuy Bui, Dae-Sik Lim, Elizabeth J Cartwright, Delvac Oceandy
Adult fibroblasts can be reprogrammed into induced pluripotent stem cells (iPSC) for use in various applications. However, there are challenges in iPSC generation including low reprogramming efficiency, yield, cell survival and viability. Since the Hippo signalling pathway is a key pathway involved in regulating cell proliferation and survival, we here test whether modification of the Hippo pathway will enhance the efficiency of iPSC generation and improve their survival. The Hippo pathway was modified by genetic ablation of the mammalian sterile-20 like kinase 1 (Mst1), a major component of the pathway...
February 27, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28257318/the-hippo-trial-a-randomized-double-blind-trial-comparing-self-gripping-parietex-progrip-mesh-and-sutured-parietex-mesh-in-lichtenstein-hernioplasty-a-long-term-follow-up-study
#20
Marijke J Molegraaf, Brechtje Grotenhuis, Bart Torensma, Victor de Ridder, Johan F Lange, Dingeman J Swank
OBJECTIVE: To evaluate the effect of a self-gripping mesh (Progrip) on the incidence of chronic postoperative inguinal pain (CPIP) and recurrence rate after Lichtenstein hernioplasty. BACKGROUND: Chronic pain is the most common complication of inguinal hernioplasty. One of the causes may be the use of sutures to secure the mesh. METHODS: Adult male patients undergoing Lichtenstein hernioplasty for a primary unilateral inguinal hernia were randomized to a self-gripping polyester mesh or a sutured polyester mesh...
March 2, 2017: Annals of Surgery
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