keyword
MENU ▼
Read by QxMD icon Read
search

MST1

keyword
https://www.readbyqxmd.com/read/28387539/expression-of-phosphorylated-hippo-pathway-kinases-mst1-2-and-lats1-2-in-her2-positive-and-triple-negative-breast-cancer-patients-treated-with-neoadjuvant-therapy
#1
Cristiana Ercolani, Anna Di Benedetto, Irene Terrenato, Laura Pizzuti, Luigi Di Lauro, Domenico Sergi, Francesca Sperati, Simonetta Buglioni, Maria Teresa Ramieri, Lucia Mentuccia, Teresa Gamucci, Letizia Perracchio, Edoardo Pescarmona, Marcella Mottolese, Maddalena Barba, Patrizia Vici, Ruggero De Maria, Marcello Maugeri-Saccà
The Hippo kinases MST1/2 and LATS1/2 inhibit the oncoproteins TAZ/YAP and regulate T cell function. Hippo kinases also cooperate with the ATR-Chk1 and ATM-Chk2 pathways, central orchestrators of the DNA damage response (DDR). We hypothesized that MST1/2 and LATS1/2 localization differently impacts the efficacy of neoadjuvant therapy (NAT) in breast cancer, being protective when expressed in the cytoplasm of tumor cells and in tumor-infiltrating lymphocytes, whereas representing molecular determinants of chemoresistance when present in the nucleus as a consequence of their cooperation with the DDR...
April 7, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28373298/mob1-mediated-phospho-recognition-in-the-core-mammalian-hippo-pathway
#2
Amber L Couzens, Shawn Xiong, James Dr Knight, Daniel Y Mao, Sebastian Guettler, Sarah Picaud, Igor Kurinov, Panagis Filippakopoulos, Frank Sicheri, Anne-Claude Gingras
The Hippo tumor suppressor pathway regulates organ size and tissue homoeostasis in response to diverse signaling inputs. The core of the pathway consists of a short kinase cascade: MST1 and MST2 phosphorylate and activate LATS1 and LATS2, which in turn phosphorylate and inactivate key transcriptional co-activators, YAP1 and TAZ (gene WWTR1). The MOB1 adapter protein regulates both phosphorylation reactions firstly by concurrently binding to the upstream MST and downstream LATS kinases to enable the trans phosphorylation reaction, and secondly by allosterically activating the catalytic function of LATS1 and LATS2 to directly stimulate phosphorylation of YAP and TAZ...
April 3, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28373297/regulation-of-protein-interactions-by-mob1-phosphorylation
#3
Shawn Xiong, Amber L Couzens, Michelle J Kean, Daniel Y Mao, Sebastian Guettler, Igor Kurinov, Anne-Claude Gingras, Frank Sicheri
MOB1 is a multifunctional protein best characterized for its integrative role in regulating Hippo and NDR pathway signaling in metazoans and the Mitotic Exit Network in yeast. Human MOB1 binds both the upstream kinases MST1 and MST2 and the downstream AGC group kinases LATS1, LATS2, NDR1 and NDR2. Binding of MOB1 to MST1 and MST2 is mediated by its phosphopeptide-binding infrastructure, the specificity of which matches the phosphorylation consensus of MST1 and MST2. On the other hand, binding of MOB1 to the LATS and NDR kinases is mediated by a distinct interaction surface on MOB1...
April 3, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28366538/morin-impedes-yap-nuclear-translocation-and-fosters-apoptosis-through-suppression-of-wnt-%C3%AE-catenin-and-nf-%C3%AE%C2%BAb-signaling-in-mst1-overexpressed-hepg2-cells
#4
NaveenKumar Perumal, MadanKumar Perumal, Anbarasu Kannan, Kumar Subramani, Devaraj Halagowder, NiranjaliDevaraj Sivasithamparam
Recent clinical and experimental evidences strongly acclaim Yes-associated protein (Yap), a key oncogenic driver in liver carcinogenesis, as a therapeutic target. Of the known multiple schemes to inhibit Yap activity, activation of Mammalian Sterile 20-like Kinase 1 (Mst1), an upstream regulator of Yap, appears to be a promising one. In this study, we hypothesize that morin, a bioflavonoid, mediates its anti-cancer effect through the activation of Mst1/hippo signaling in liver cancer cells. To test this hypothesis, both full length Mst1 (F-Mst1) and kinase active N-terminal Mst1 (N-Mst1)-overexpressed HepG2 cells were used...
March 31, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28327630/rassf-proteins-as-modulators-of-mst1-kinase-activity
#5
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/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
#6
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...
April 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28245464/the-hippo-signaling-pathway-regulates-ovarian-function-via-the-proliferation-of-ovarian-germline-stem-cells
#7
Haifeng Ye, Xiaoyan Li, Tuochen Zheng, Chuan Hu, Zezheng Pan, Jian Huang, Jia Li, Wei Li, Yuehui Zheng
OBJECTIVE: To improve the separation, identification and cultivation of ovarian germline stem cells (OGSCs), to clarify the relationship between the Hippo signaling pathway effector YAP1 and the proliferation and differentiation of OGSCs in vitro and to identify the major contribution of Hippo signaling to ovarian function. METHODS: Two-step enzymatic separation processes and magnetic separation were used to isolate and identify OGSCs by determining the expression of Mvh, Oct4, Nanog, Fragilis and Stella markers...
February 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28210902/deletion-of-mammalian-sterile-20-like-kinase-1-attenuates-neuronal-loss-and-improves-locomotor-function-in-a-mouse-model-of-spinal-cord-trauma
#8
Pan-Feng Wang, Da-Yuan Xu, Yuntong Zhang, Xiao-Bin Liu, Yan Xia, Pan-Yu Zhou, Qing-Ge Fu, Shuo-Gui Xu
Neuronal cell death following spinal cord injury (SCI) is an important contributor to neurological deficits. The purpose of our work was to delineate the function of mammalian sterile 20-like kinase 1 (Mst1), a pro-apoptotic kinase and key mediator of apoptotic signaling, in the pathogenesis of an experimental mouse model of SCI. Male mice received a mid-thoracic spinal contusion injury, and it was found that phosphorylation of Mst1 at the injured site was enhanced significantly following SCI. Furthermore, when compared to the wild-type controls, Mst1-deficient mice displayed improved locomotor function by increased Basso mouse scale score...
February 16, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28197608/the-dynamic-mechanism-of-rassf5-and-mst-kinase-activation-by-ras
#9
Tsung-Jen Liao, Hyunbum Jang, Chung-Jung Tsai, David Fushman, Ruth Nussinov
As a tumor suppressor, RASSF5 (NORE1A) activates MST1/2 thereby modulating the Hippo pathway. Structurally, activation involves RASSF5 and MST1/2 swapping their SARAH domains to form a SARAH heterodimer. This exposes the MST1/2 kinase domain which homodimerizes, leading to trans-autophosphorylation. The SARAH-SARAH interaction shifts RASSF5 away from its autoinhibited state and relieves MST1/2 autoinhibition. Separate crystal structures are available for the RA (Ras association) domain and SARAH dimer, where SARAH is a long straight α-helix...
March 1, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28183853/mark4-inhibits-hippo-signaling-to-promote-proliferation-and-migration-of-breast-cancer-cells
#10
Emad Heidary Arash, Ahmed Shiban, Siyuan Song, Liliana Attisano
The Hippo pathway is a critical regulator of tissue size, and aberrations in pathway regulation lead to cancer. MST1/2 and LATS1/2 kinases comprise the core of the pathway that, in association with adaptor proteins SAV and MOB, functions in a sequential manner to phosphorylate and inhibit the transcription factors YAP and TAZ. Here we identify mammalian MARK family members as activators of YAP/TAZ. We show that depletion of MARK4 in MDA-MB-231 breast cancer cells results in the loss of nuclear YAP/TAZ and decreases the expression of YAP/TAZ targets...
March 2017: EMBO Reports
https://www.readbyqxmd.com/read/28169360/loss-of-dlg5-promotes-breast-cancer-malignancy-by-inhibiting-the-hippo-signaling-pathway
#11
Jie Liu, Juan Li, Pingping Li, Yaochun Wang, Zheyong Liang, Yina Jiang, Jing Li, Chen Feng, Ruiqi Wang, He Chen, Can Zhou, Jianmin Zhang, Jin Yang, Peijun Liu
Discs Large Homolog 5 (DLG5) plays an important role in the maintenance of epithelial cell polarity. Recent research showed that DLG5 is decreased in Yes-associated protein (YAP)-overexpressing cells. However, the exact relationship between DLG5 and YAP is not clear. In this study, we showed that loss of DLG5 promoted breast cancer cell proliferation by inhibiting the Hippo signaling pathway and increasing nuclear YAP expression. Furthermore, depletion of DLG5 induced epithelial-mesenchymal transition (EMT) and disrupted epithelial cell polarity, which was associated with altered expression of Scribble, ZO1, E-cadherin and N-cadherin and their mislocalization...
February 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28150487/structural-insights-into-the-regulation-of-hippo-signaling
#12
Leah Cairns, Thao Tran, Jennifer M Kavran
During development, the Hippo pathway regulates the balance between cell proliferation and apoptosis to control organ size. Appropriate Hippo signaling is associated with stem cell maintenance, while inappropriate signaling can result in tumorigenesis and cancer. Cellular and genetic investigations have identified core components and determined that complex formation and protein phosphorylation are crucial regulatory events. The recent spate of high-resolution structures of Hippo pathway components have begun to reveal the molecular mechanisms controlling these events, including the molecular determinates of complex formation between YAP and TEAD, the role of phosphorylation in controlling complex formation by Mob, and the conformational changes accompanying Mst1/2 kinase domain activation...
February 9, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28145433/dendritic-cell-mst1-inhibits-th17-differentiation
#13
Chunxiao Li, Yujing Bi, Yan Li, Hui Yang, Qing Yu, Jian Wang, Yu Wang, Huilin Su, Anna Jia, Ying Hu, Linian Han, Jiangyuan Zhang, Simin Li, Wufan Tao, Guangwei Liu
Although the differentiation of CD4(+)T cells is widely studied, the mechanisms of antigen-presenting cell-dependent T-cell modulation are unclear. Here, we investigate the role of dendritic cell (DC)-dependent T-cell differentiation in autoimmune and antifungal inflammation and find that mammalian sterile 20-like kinase 1 (MST1) signalling from DCs negatively regulates IL-17 producing-CD4(+)T helper cell (Th17) differentiation. MST1 deficiency in DCs increases IL-17 production by CD4(+)T cells, whereas ectopic MST1 expression in DCs inhibits it...
February 1, 2017: Nature Communications
https://www.readbyqxmd.com/read/28141542/kinetic-characterization-of-apoptotic-ras-signaling-through-nore1-mst1-complex-formation
#14
Agne Koturenkiene, Cihan Makbul, Christian Herrmann, Diana Constantinescu-Aruxandei
Ras-mediated apoptotic signaling is expected to be mediated via Rassf-MST complexes, but the system has been poorly characterized in vitro until now. Here we demonstrate that active H-Ras, Nore1A and MST1 form a stable ternary complex in vitro without other external factors, Nore1A interacting simultaneously with H-Ras and MST1 via its RBD and SARAH domain, respectively. Moreover, our data show for the first time that the SARAH domain of Nore1A plays a role in the Nore1A binding to H-Ras. Finally, we analyze the relation between the electrostatic and hydrophobic forces and kinetic constants of the Nore1A - H-Ras complex...
May 1, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28139652/lnc-ing-ror1-her3-and-hippo-signalling-in-metastasis
#15
Wei Zhuo, Yibin Kang
Long noncoding RNAs (lncRNAs) are increasingly recognized for their role in cancer progression. The previously uncharacterized lncRNA MAYA is now shown to promote bone metastasis by bridging ROR1-HER3 and Hippo-YAP pathways. Neuregulin-induced HER3 phosphorylation by ROR1 recruits a MAYA-containing protein complex to methylate Hippo/MST1 and activate YAP target genes that are essential for bone metastasis.
January 31, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28137909/ndr1-dependent-regulation-of-kindlin-3-controls-high-affinity-lfa-1-binding-and-immune-synapse-organization
#16
Naoyuki Kondo, Yoshihiro Ueda, Toshiyuki Kita, Madoka Ozawa, Takashi Tomiyama, Kaneki Yasuda, Dae-Sik Lim, Tatsuo Kinashi
Antigen-specific adhesion between T cells and antigen-presenting cells (APC) during the formation of the immunological synapse (IS) is mediated by LFA-1 and ICAM-1. Here, LFA-1-ICAM-1 interactions were measured at the single-molecule level on supported lipid bilayers. High-affinity binding was detected at low frequencies in the inner peripheral supramolecular activation cluster (SMAC) zone that contained high levels of activated Rap1 and kindlin-3. Rap1 was essential for T cell attachment, whereas deficiencies of ste20-like kinases, Mst1/Mst2, diminished high-affinity binding and abrogated central SMAC (cSMAC) formation with mislocalized kindlin-3 and vesicle transport regulators involved in T cell receptor recycling/releasing machineries, resulting in impaired T cell-APC interactions...
April 15, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28129359/high-throughput-characterization-of-blood-serum-proteomics-of-ibd-patients-with-respect-to-aging-and-genetic-factors
#17
Antonio F Di Narzo, Shannon E Telesco, Carrie Brodmerkel, Carmen Argmann, Lauren A Peters, Katherine Li, Brian Kidd, Joel Dudley, Judy Cho, Eric E Schadt, Andrew Kasarskis, Radu Dobrin, Ke Hao
To date, no large scale, systematic description of the blood serum proteome has been performed in inflammatory bowel disease (IBD) patients. By using microarray technology, a more complete description of the blood proteome of IBD patients is feasible. It may help to achieve a better understanding of the disease. We analyzed blood serum profiles of 1128 proteins in IBD patients of European descent (84 Crohn's Disease (CD) subjects and 88 Ulcerative Colitis (UC) subjects) as well as 15 healthy control subjects, and linked protein variability to patient age (all cohorts) and genetic components (genotype data generated from CD patients)...
January 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28114269/a-ror1-her3-lncrna-signalling-axis-modulates-the-hippo-yap-pathway-to-regulate-bone-metastasis
#18
Chunlai Li, Shouyu Wang, Zhen Xing, Aifu Lin, Ke Liang, Jian Song, Qingsong Hu, Jun Yao, Zhongyuan Chen, Peter K Park, David H Hawke, Jianwei Zhou, Yan Zhou, Shuxing Zhang, Han Liang, Mien-Chie Hung, Gary E Gallick, Leng Han, Chunru Lin, Liuqing Yang
Bone metastases remain a serious health concern because of limited therapeutic options. Here, we report that crosstalk between ROR1-HER3 and the Hippo-YAP pathway promotes breast cancer bone metastasis in a long noncoding RNA-dependent fashion. Mechanistically, the orphan receptor tyrosine kinase ROR1 phosphorylates HER3 at a previously unidentified site Tyr1307, following neuregulin stimulation, independently of other ErbB family members. p-HER3 Tyr1307 recruits the LLGL2-MAYA-NSUN6 RNA-protein complex to methylate Hippo/MST1 at Lys59...
February 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28099921/stiehopus-japonieus-acidic-mucopolysaccharide-inhibits-the-proliferation-of-pancreatic-cancer-sw1990-cells-through-hippo-yap-pathway
#19
Xiaoyu Li, Yi Liu, Cuiping Zhang, Qinghui Niu, Hui Wang, Cong Che, Man Xie, Bin Zhou, Yonghong Xu, Qi Zhang, Jun Wu, Zibin Tian
Previous studies have indicated that stiehopus japonieus acidic mucopolysaccharide (SJAMP) could inhibit the proliferation of pancreatic cancer cell SW1990. However, the mechanism remains unclear. In our study, YAP expression was identified by immunohistochemistry and quantitative Real-time PCR from 45 pairs of human pancreatic ductal adenocarcinoma (PDAC) tissues and their adjacent non-tumor samples. We found that the YAP expression was associated with the histological differentiation degree, and negatively correlated with pancreatic cancer patients' survival...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28087714/dlg5-connects-cell-polarity-and-hippo-signaling-protein-networks-by-linking-par-1-with-mst1-2
#20
Julian Kwan, Anna Sczaniecka, Emad Heidary Arash, Liem Nguyen, Chia-Chun Chen, Srdjana Ratkovic, Olga Klezovitch, Liliana Attisano, Helen McNeill, Andrew Emili, Valeri Vasioukhin
Disruption of apical-basal polarity is implicated in developmental disorders and cancer; however, the mechanisms connecting cell polarity proteins with intracellular signaling pathways are largely unknown. We determined previously that membrane-associated guanylate kinase (MAGUK) protein discs large homolog 5 (DLG5) functions in cell polarity and regulates cellular proliferation and differentiation via undefined mechanisms. We report here that DLG5 functions as an evolutionarily conserved scaffold and negative regulator of Hippo signaling, which controls organ size through the modulation of cell proliferation and differentiation...
December 15, 2016: Genes & Development
keyword
keyword
100906
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"