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MST1

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https://www.readbyqxmd.com/read/28534197/pcmt1-ameliorates-neuronal-apoptosis-by-inhibiting-the-activation-of-mst1-after-subarachnoid-hemorrhage-in-rats
#1
Ligen Shi, Ammar Al-Baadani, Keren Zhou, Anwen Shao, Shenbin Xu, Sheng Chen, Jianmin Zhang
Mammalian sterile 20-like kinase 1 (MST1) is found to promote neuronal apoptosis. Protein-L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1), an anti-apoptosis factor, was recently identified as an MST1-interacting protein. This study aims to explore the potential role of PCMT1 in reducing MST1-induced neuronal apoptosis after subarachnoid hemorrhage (SAH) in rats. One hundred ninety-eight male Sprague-Dawley rats were used. An exogenous PCMT1 agonist, CGP 3466B, was injected subcutaneously 1 h after the SAH induced by endovascular perforation...
May 22, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28527887/mst1-deficiency-promotes-b-cell-responses-by-cd4-t-cell-derived-il-4-resulting-in-hypergammaglobulinemia
#2
Eunchong Park, Myun Soo Kim, Ju Han Song, Kyung Min Cho, Kyung-Hye Roh, Rana Lee, Tae Sung Kim
MST1 deficiency causes T and B cell lymphopenia, resulting in combined immunodeficiency. However, MST1-deficient patients also exhibit autoimmune-like symptoms such as hypergammaglobulinemia and autoantibody production. Recent studies have shown that the autoimmune responses observed in MST1-deficient patients were most likely attributable to defective regulatory T (Treg) cells instead of intrinsic signals in MST1-lacking B cells. Nevertheless, it is not determined how MST1 deficiency in T cells breaks B cell tolerance and causes systemic autoimmune-like phenotypes...
May 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28487214/eif4e-phosphorylation-by-mst1-reduces-translation-of-a-subset-of-mrnas-but-increases-lncrna-translation
#3
Kyung-Won Min, Sylvia Davila, Richard W Zealy, Lawson T Lloyd, In Young Lee, Rumi Lee, Kyung Hye Roh, Ahjin Jung, Jacek Jemielity, Eui-Ju Choi, Jeong Ho Chang, Je-Hyun Yoon
Post-transcriptional gene regulation is an important step in eukaryotic gene expression. The last step to govern production of nascent peptides is during the process of mRNA translation. mRNA translation is controlled by many translation initiation factors that are susceptible to post-translational modifications. Here we report that one of the translation initiation factors, eIF4E, is phosphorylated by Mammalian Ste20-like kinase (MST1). Upon phosphorylation, eIF4E weakly interacts with the 5' CAP to inhibit mRNA translation...
May 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28487119/the-mammalian-ste20-like-kinase-1-mst1-is-a-substrate-for-the-apoptosis-inhibiting-protein-kinase-ck2
#4
Christina Servas, Sandra Kiehlmeier, Julia Hach, Rebecca Gross, Claudia Götz, Mathias Montenarh
Apoptosis and the response to cell stress are evolutionary highly conserved mechanisms. Both processes require strict regulation, which is often performed by protein kinases. The mammalian Sterile 20-like kinase 1 (MST1) is a pro-apoptotic protein kinase, which is activated and cleaved by caspases upon the induction of cell stress. Being a phosphoprotein itself, the activity of MST1 is regulated by phosphorylation. Protein kinase CK2 is an anti-apoptotic protein kinase which seems to be involved in the regulation of many different cellular processes including apoptosis...
May 6, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28480597/melatonin-protects-against-diabetic-cardiomyopathy-through-mst1-sirt3-signaling
#5
Mingming Zhang, Jie Lin, Shanjie Wang, Zheng Cheng, Jianqiang Hu, Tingting Wang, Wanrong Man, Tao Yin, Wenyi Guo, Erhe Gao, Russel J Reiter, Haichang Wang, Dongdong Sun
The present study investigated the effects of melatonin on diabetic cardiomyopathy (DCM) and determined the underlying mechanisms. Echocardiography indicated that melatonin notably mitigated the adverse left ventricle remodeling and alleviated cardiac dysfunction in DCM. The mechanisms were attributed to increased autophagy, reduced apoptosis and alleviated mitochondrial dysfunction. Furthermore, melatonin inhibited Mst1 phosphorylation and promoted Sirt3 expression in DCM. These results indicated that melatonin may exert its effects through Mst1/ Sirt3 signaling...
May 8, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28469576/plant-produced-asialo-erythropoietin-restores-pancreatic-beta-cell-function-by-suppressing-mammalian-sterile-20-like-kinase-mst1-and-caspase-3-activation
#6
Elena Arthur, Farooqahmed S Kittur, Yuan Lin, Chiu-Yueh Hung, David C Sane, Jiahua Xie
Pancreatic beta-cell death adversely contributes to the progression of both type I and II diabetes by undermining beta-cell mass and subsequently diminishing endogenous insulin production. Therapeutics to impede or even reverse the apoptosis and dysfunction of beta-cells are urgently needed. Asialo-rhuEPO, an enzymatically desialylated form of recombinant human erythropoietin (rhuEPO), has been shown to have cardioprotective and neuroprotective functions but with no adverse effects like that of sialylated rhuEPO...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28465479/kctd11-inhibits-growth-and-metastasis-of-hepatocellular-carcinoma-through-activating-hippo-signaling
#7
Rongliang Tong, Beng Yang, Heng Xiao, Chuanhui Peng, Wendi Hu, Xiaoyu Weng, Shaobing Cheng, Chengli Du, Zhen Lv, Chaofeng Ding, Lin Zhou, Haiyang Xie, Jian Wu, Shusen Zheng
A lack of effective prognostic biomarkers and molecular targets is a serious problem in hepatocellular carcinoma. KCTD11, reported as a tumor suppressor, are still not well understood. In this study, KCTD11 was found low-expressed in HCC tissues and cell lines. The HCC patients with low expression of KCTD11 suggested shorter overall survival. We found KCTD11 inhibiting cell proliferation in vitro and tumor growth in vivo, by activating p21 and repressing cycle related proteins. KCTD11 also inhibited cell adhesion by decreasing CTGF and CLDN1...
April 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28454447/inhibitory-effect-and-mechanism-of-exogenous-mammalian-sterile-20-like-kinase-1-on-the-growth-of-human-colorectal-cancer
#8
Jian Wu, Xiaohong Yang, Hongfei Lu, Liqiao Liu, Baohua Xu, Shuangyan Zheng, Bo Yu, Kemin Jie, Fusheng Wan
The present study aimed to observe the inhibitory effect and preliminary mechanism of exogenous mammalian sterile 20-like kinase 1 (MST1) on the growth of colorectal cancer SW480 cells. The SW480 cells were randomly divided into the following groups: Control, empty enhanced green fluorescent protein (EGFP) plasmid (pEGFP-N1), MST1 EGFP plasmid (pEGFP-MST1), 20 µmol/l fluorouracil (5-FU) and pEGFP-MST1 + 5-FU. An MTS colorimetric assay was used to detect cell viability, Hoechst 33342 staining was used to observe cell apoptosis, and western blotting and immunohistochemistry were used to detect the levels of the proteins MST1, yes-associated protein (YAP), phospho-YAP1 (Ser127), p53 and p53 upregulated modulator of apoptosis (PUMA)...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28448802/ddk-promotes-tumor-chemoresistance-and-survival-via-multiple-pathways
#9
Nanda Kumar Sasi, Arjun Bhutkar, Nathan J Lanning, Jeffrey P MacKeigan, Michael Weinreich
DBF4-dependent kinase (DDK) is a two-subunit kinase required for initiating DNA replication at individual origins and is composed of CDC7 kinase and its regulatory subunit DBF4. Both subunits are highly expressed in many diverse tumor cell lines and primary tumors, and this is correlated with poor prognosis. Inhibiting DDK causes apoptosis of tumor cells, but not normal cells, through a largely unknown mechanism. Firstly, to understand why DDK is often overexpressed in tumors, we identified gene expression signatures that correlate with DDK high- and DDK low-expressing lung adenocarcinomas...
May 2017: Neoplasia: An International Journal for Oncology Research
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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...
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
#17
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
#18
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
#19
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
#20
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
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