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https://www.readbyqxmd.com/read/27913678/regulation-of-protein-phosphatase-2a-pp2a-tumor-suppressor-function-by-pme-1
#1
REVIEW
Amanpreet Kaur, Jukka Westermarck
Protein phosphatase 2A (PP2A) plays a major role in maintaining cellular signaling homeostasis by dephosphorylation of a variety of signaling proteins and acts as a tumor suppressor. Protein phosphatase methylesterase-1 (PME-1) negatively regulates PP2A activity by highly complex mechanisms that are reviewed here. Importantly, recent studies have shown that PME-1 promotes oncogenic MAPK/ERK and AKT pathway activities in various cancer types. In human glioma, high PME-1 expression correlates with tumor progression and kinase inhibitor resistance...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27913436/erk-and-p38-mapk-activities-determine-sensitivity-to-pi3k-mtor-inhibition-via-regulation-of-myc-and-yap
#2
Taru Muranen, Laura M Selfors, Julie Hwang, Lisa L Gallegos, Jonathan L Coloff, Carson C Thoreen, Seong A Kang, David M Sabatini, Gordon B Mills, Joan S Brugge
Aberrant activation of the PI3K/mTOR pathway is a common feature of many cancers and an attractive target for therapy, but resistance inevitably evolves as is the case for any cancer cell-targeted therapy. In animal tumor models, chronic inhibition of PI3K/mTOR initially inhibits tumor growth, but over time, tumor cells escape inhibition. In this study, we identified a context-dependent mechanism of escape whereby tumor cells upregulated the proto-oncogene transcriptional regulators c-MYC and YAP1. This mechanism was dependent on both constitutive ERK activity as well as inhibition of the stress kinase p38...
October 20, 2016: Cancer Research
https://www.readbyqxmd.com/read/27913297/phospholipase-c%C3%AE-1-suppresses-foreign-body-giant-cell-formation-by-maintaining-runx1-expression-in-macrophages
#3
Ye Seon Kim, Chang Youp Ok, Joon Seong Park, Ha Young Lee, Yoe-Sik Bae
Foreign body giant cell (FBGC) formation is associated with the inflammatory response following material implantation. However, the intracellular signaling events that regulate the process remain unclear. Here, we investigated the potential role of phospholipase C (PLC)γ1, a crucial enzyme required for growth factor-induced signaling, on FBGC formation. Knock-down of PLCγ1 using shRNA induced FBGC formation accompanied by increased expression of cathepsin K, DC-STAMP and CD36. Re-addition of PLCγ1 decreased FBGC formation...
November 29, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27913296/regulation-of-skeletal-muscle-insulin-stimulated-signaling-through-the-mek-redd1-mtor-axis
#4
Cory M Dungan, David L Williamson
Recent findings in adipocytes suggest that mitogen-activated protein kinase (MAPK)/extracellular-regulated signaling kinase (ERK) kinase 1/2 (MEK1/2) signaling regulates regulated in development and DNA damage 1 (REDD1) protein expression. Similarly, our previous work show that a lack of REDD1 protein expression, and associated hyperactive basal mechanistic target of rapamycin (mTOR) signaling, limits skeletal muscle's response to insulin. Therefore, we sought to determine: 1) if MEK1/2 inhibition is sufficient to reduce REDD1 protein expression and subsequently insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation via negative feedback of hyperactive mTOR in REDD1 wild-type (WT) mice and 2) if rapamycin-mediated mTOR inhibition is sufficient to improve IRS-1 tyrosine phosphorylation in REDD1 knockout (KO) mice...
November 29, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27913220/mapk-erk-activity-is-required-for-the-successful-progression-of-mitosis-in-sea-urchin-embryos
#5
Mulner-Lorillon Odile, Chassé Héloïse, Morales Julia, Bellé Robert, Cormier Patrick
Using sea urchin embryos, we demonstrate that the MEK/MAPK/ERK cascade is essential for the proper progression of the cell cycle. Activation of a limited fraction of MAPK/ERK is required between S-phase and M-phase. Neither DNA replication nor CDK1 activation are impacted by the inhibition of this small active MAPK/ERK fraction. Nonetheless, the chromatin and spindle organisations are profoundly altered. Early morphological disorders induced by the absence of MAPK/ERK activation are correlated with an important inhibition of global protein synthesis and modification in the cyclin B accumulation profile...
November 29, 2016: Developmental Biology
https://www.readbyqxmd.com/read/27913219/tbx2-regulates-anterior-neural-specification-by-repressing-fgf-signaling-pathway
#6
Gun-Sik Cho, Dong-Seok Park, Sun-Cheol Choi, Jin-Kwan Han
During early embryogenesis, FGF signals regulate the antero-posterior (AP) patterning of the neural plate by promoting posterior cell fates. In particular, BMP signal-mediated attenuation of FGF pathway plays a critical role in the determination of the anterior neural region. Here we show that Tbx2, a T-box transcriptional repressor regulates anterior neural specification by suppressing FGF8 signaling pathway in Xenopus embryo. Tbx2 is expressed in the anterior edge of the neural plate in early neurulae. Overexpression and knockdown of Tbx2 induce expansion and reduction in the expression of anterior neural markers, respectively...
November 29, 2016: Developmental Biology
https://www.readbyqxmd.com/read/27912883/miltirone-protects-human-ea-hy926-endothelial-cells-from-oxidized-low-density-lipoprotein-derived-oxidative-stress-via-a-heme-oxygenase-1-and-mapk-nrf2-dependent-pathway
#7
Liu Zhang, Hui Zhang, Xueyan Li, Bingjie Jia, Yuyu Yang, Ping Zhou, Ping Li, Jun Chen
BACKGROUND: Oxidized low-density lipoprotein (ox-LDL) is an underlying cause of endothelial dysfunction, which is an early event in the pathogenesis of atherosclerosis. In our previous study, we established an ARE-driven luciferase reporter system and screened out several potential Nrf2 activators from Salvia miltiorrhiza Bunge. PURPOSE: Since miltirone showed the most potent ARE-driven luciferase activity, the aim of this study was to test the protective role of miltirone against oxidative stress in endothelial cell and to investigate the underlying mechanistic signaling pathways...
December 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27912102/toyocamycin-induces-apoptosis-via-the-crosstalk-between-reactive-oxygen-species-and-p38-erk-mapks-signaling-pathway-in-human-prostate-cancer-pc-3-cells
#8
Sul-Gi Park, Sang-Hun Kim, Kwang-Youn Kim, Sun-Nyoung Yu, Hyeun-Deok Choi, Young-Wook Kim, Hyo-Won Nam, Young-Kyo Seo, Soon-Cheol Ahn
BACKGROUND: Toyocamycin, an antibiotic agent isolated from Streptomyces species, has been shown to have anticancer and chemopreventive effects on various cancer cells. Until now, Toyocamycin-induced apoptosis has not been reported to be involved in the regulation between mitogen-activated protein kinases (MAPKs) and reactive oxygen species (ROS) production. METHODS: Cell viability assay, western blot, cell-cycle arrest, annexin V/propidium iodide assay, reactive oxygen species (ROS) production, mitochondrial membrane potential and intracellular Ca(2+) flux were assayed...
October 24, 2016: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/27911862/overexpression-of-semaphorin-3e-enhances-pancreatic-cancer-cell-growth-and-associates-with-poor-patient-survival
#9
Lin-Kin Yong, Syeling Lai, Zhengdong Liang, Ethan Poteet, Fengju Chen, George van Buren, William Fisher, Qianxing Mo, Changyi Chen, Qizhi Yao
Semaphorin-3E (Sema3E) is a member of an axon guidance gene family, and has recently been reported to contribute to tumor progression and metastasis. However, its role in pancreatic cancer is yet unknown and uncharacterized. In this study, we showed that Sema3E is overexpressed in human pancreatic cancer, and that high Sema3E levels are associated with tumor progression and poor survival. Interestingly, we also observed Sema3E expression in the nucleus, even though Sema3E is reported to be a secreted protein...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911794/activation-of-mutant-tert-promoter-by-ras-erk-signaling-is-a-key-step-in-malignant-progression-of-braf-mutant-human-melanomas
#10
Yinghui Li, Hui Shan Cheng, Wee Joo Chng, Vinay Tergaonkar
Although activating BRAF/NRAS mutations are frequently seen in melanomas, they are not sufficient to drive malignant transformation and require additional events. Frequent co-occurrence of mutations in the promoter for telomerase reverse transcriptase (TERT), along with BRAF alterations, has recently been noted and correlated with poorer prognosis, implicating a functional link between BRAF signaling and telomerase reactivation in melanomas. Here, we report that RAS-ERK signaling in BRAF mutant melanomas is critical for regulating active chromatin state and recruitment of RNA polymerase II at mutant TERT promoters...
November 23, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27910068/endometrial-carcinoma-specific-targeted-pathways
#11
Nuria Eritja, Andree Yeramian, Bo-Juen Chen, David Llobet-Navas, Eugenia Ortega, Eva Colas, Miguel Abal, Xavier Dolcet, Jaume Reventos, Xavier Matias-Guiu
Endometrial cancer (EC) is the most common gynecologic malignancy in the western world with more than 280,000 cases per year worldwide. Prognosis for EC at early stages, when primary surgical resection is the most common initial treatment, is excellent. Five-year survival rate is around 70 %.Several molecular alterations have been described in the different types of EC. They occur in genes involved in important signaling pathways. In this chapter, we will review the most relevant altered pathways in EC, including PI3K/AKT/mTOR, RAS-RAF-MEK-ERK, Tyrosine kinase, WNT/β-Catenin, cell cycle, and TGF-β signaling pathways...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27909955/suppressive-effects-of-dabrafenib%C3%A2-on-endothelial-protein-c-receptor-shedding
#12
Sae-Kwang Ku, Jongdoo Kim, Sang Chan Kim, Jong-Sup Bae
Beyond its role in the activation of protein C, the endothelial cell protein C receptor (EPCR) plays an important role in the cytoprotective pathway. EPCR can be shed from the cell surface, which is mediated by tumor necrosis factor-α converting enzyme (TACE). Dabrafenib (DAB) is a B-Raf inhibitor and initially used for the treatment of metastatic melanoma therapy. However, little is known about the effects of DAB on EPCR shedding. We investigated this issue by monitoring the effects of DAB on phorbol-12-myristate 13-acetate (PMA)-, tumor necrosis factor (TNF)-α-, interleukin (IL)-1β-induced EPCR shedding in human umbilical vein endothelial cells (HUVECs), and cecal ligation and puncture (CLP)-mediated EPCR shedding in mice and underlying mechanism...
December 1, 2016: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/27909724/hsp27-regulates-tgf-%C3%AE-mediated-lung-fibroblast-differentiation-through-the-smad3-and-erk-pathways
#13
Gang Wang, Hao Jiao, Jun-Nian Zheng, Xia Sun
Idiopathic pulmonary fibrosis (IPF) is a chronic lethal interstitial lung disease with unknown etiology. Recent studies have indicated that heat-shock protein 27 (HSP27) contributes to the pathogenesis of IPF through the regulation of epithelial-mesenchymal transition (EMT). However, the expression and role of HSP27 in fibroblasts during pulmonary fibrogenesis has not been investigated to date, at least to the best of our knowledge. In this study, we examined the expression of HSP27 in fibrotic lung tissue and fibroblasts from bleomycin (BLM)-challenged mice and human lung fibroblasts treated with transforming growth factor-β (TGF-β)...
November 28, 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27909249/mortalin-mediated-and-erk-controlled-targeting-of-hif-1%C3%AE-to-mitochondria-confers-resistance-to-apoptosis-under-hypoxia
#14
Ilias Mylonis, Maria Kourti, Martina Samiotaki, George Panayotou, George Simos
Hypoxia inducible factor-1 (HIF-1) is the main transcriptional activator of the cellular response to hypoxia and an important target of anticancer therapy. Phosphorylation by ERK stimulates the transcriptional activity of HIF-1α by inhibiting its CRM1-dependent nuclear export. Here, we demonstrate that phosphorylation by ERK also regulates the association of HIF-1α with a novel interaction partner identified as mortalin (GRP75) which mediates non-genomic involvement of HIF-1α in apoptosis. Mortalin binds specifically to HIF-1α lacking modification by ERK and their complex is localized outside the nucleus...
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27909054/identification-of-a-substrate-selective-exosite-within-the-metalloproteinase-anthrax-lethal-factor
#15
Allison B Goldberg, Eunice Cho, Chad J Miller, Hua Jane Lou, Benjamin E Turk
The metalloproteinase anthrax lethal factor (LF) is secreted by Bacillus anthracis to promote disease virulence through disruption of host signaling pathways. LF is a highly specific protease, exclusively cleaving mitogen-activated protein kinase kinases (MKKs) and rodent NACHT leucine-rich repeat and pyrin domain containing protein 1B (NLRP1B). How LF achieves such restricted substrate specificity is not understood. Previous studies have suggested the existence of an exosite interaction between LF and MKKs that promotes cleavage efficiency and specificity...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27908723/oxidation-inhibits-pth-receptor-signaling-and-trafficking
#16
Juan A Ardura, Verónica Alonso, Pedro Esbrit, Peter A Friedman
Reactive Oxygen Species (ROS) increase during aging, potentially affecting many tissues including brain, heart, and bone. ROS alter signaling pathways and constitute potential therapeutic targets to limit oxidative damaging effects in aging-associated diseases. Parathyroid hormone receptors (PTHR) are widely expressed and PTH is the only anabolic therapy for osteoporosis. The effects of oxidative stress on PTHR signaling and trafficking have not been elucidated. Here, we used Fluorescence Resonance Energy Transfer (FRET)-based cAMP, ERK, and calcium fluorescent biosensors to analyze the effects of ROS on PTHR signaling and trafficking by live-cell imaging...
November 28, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27908706/highly-expressed-nrsn2-is-related-to-malignant-phenotype-in-ovarian-cancer
#17
Wenbin Tang, Aimin Ren, Hongyang Xiao, Huizhen Sun, Bin Li
Neurensin-2 (NRSN2) is a 24KD protein, which is reported located in the membrane, while its biological functions remain unknown, not to mention in the field of tumor biology. In current study, we aimed to analyze the functions of NRSN2 in ovarian cancer. We screened TCGA database and surprisingly found that its copy number and mRNA level are gained and heightened respectively in parts of serous ovarian cancer patients. In current study, both loss- and gain- function assays found that NRSN2 is associated with the malignant phenotype in ovarian cancer cells, because NRSN2 plays a remarkable role in anchorage-independent colony formation, subcutaneous tumor formation, cell invasion, and chemoresistance...
November 28, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27908199/hemoglobin-extravasation-in-the-brain-of-rats-exchange-transfused-with-hemoglobin-based-oxygen-carriers
#18
Laura Terraneo, Paola Bianciardi, Ashok Malavalli, Gnel Mkrtchyan, Stephanie N Spann, Jeff Lohman, Michele Samaja, Kim D Vandegriff
Haemoglobin (Hb)-based oxygen carriers are under consideration as oxygen therapeutics. Their effect on apoptosis is critical, because the onset of pro-apoptotic pathways may lead to tissue damage. MP4OX, a polyethylene glycol-conjugated human Hb preserves the baseline level of neuron apoptosis with respect to sham. Here we develop a method for measuring Hb extravasation in brain. We exchange transfused rats by haemorrhaging 50% of their blood with simultaneous, isovolemic replacement with Hextend (negative control), MP4OX, or αα-cross-linked Hb...
December 1, 2016: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/27907835/inhibition-of-the-p38-mapk-signaling-pathway-suppresses-the-apoptosis-and-expression-of-proinflammatory-cytokines-in-human-osteoarthritis-chondrocytes
#19
He-Yan Sun, Kong-Zu Hu, Zong-Sheng Yin
This study aims to investigate the effects of p38-MAPK signaling pathway on the apoptosis and expression of proinflammatory cytokines in human osteoarthritis (OA) chondrocytes. Human articular cartilage specimens were obtained from 57 OA patients and 31 patients with lower extremity traumatic amputations. The expressions of p38-MAPK pathway-related proteins in cartilage tissue were detected by immunochemistry. Cultured chondrocytes isolated from human OA cartilage were assigned into the blank group, the IL-1β group, the PD (PD980959, ERK pathway inhibitors)+IL-1β group, the SB (SB203580, p38 pathway inhibitors)+IL-1β group, and the SP (SP600125, JNK signaling pathway inhibitors)+IL-1β group...
November 28, 2016: Cytokine
https://www.readbyqxmd.com/read/27905842/airway-smooth-muscle-cells-from-ovalbumin-sensitized-mice-show-increased-proliferative-response-to-tgf%C3%AE-1-due-to-up-regulation-of-smad3-and-tgf%C3%AE-rii
#20
Jianting Shi, Ming Chen, Lihua Ouyang, Linjie Huang, Xiaoling Lin, Wei Zhang, Ruiyun Liang, Zhiqiang Lv, Shanying Liu, Shanping Jiang
Transforming growth factor (TGF)-β1 is an important cytokine in airway remodeling in asthma. However, results of studies focusing on the effect of TGFβ1 on proliferation of airway smooth muscle cells (ASMCs) are controversial. This study aimed to elucidate the role of TGFβ1 signaling in the proliferation of ASMCs by establishing an allergic model that mimics airway remodeling in chronic asthma and cell culture. Cell proliferation was detected by viable cell counting and Cell Counting Kit (CCK)-8 analysis...
December 1, 2016: Journal of Asthma: Official Journal of the Association for the Care of Asthma
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