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https://www.readbyqxmd.com/read/27922189/optimal-arac-cytotoxicity-to-aml-cells-requires-erk5-activity
#1
Ruifang Zheng, George P Studzinski
Cytarabine (AraC) has been the primary treatment agent for Acute Myeloid Leukemia (AML) in the past 30 years, but the precise mechanism of its action is not completely known. Here we assessed the role of ERK5 in AraC-induced cell death in AML cell lines HL60 and U937 using ERK5 inhibitors BIX02189 and XMD8-92. We report that inhibition of MEK5/ERK5 activity reduces AraC-induced cell death, DNA damage, the upregulated DNA damage biomarkers, and produced G2 phase cell cycle arrest. In addition, the pro-survival protein P-Bcl2 Ser70 was found to be associated with decreased AraC-induced cell death following XMD8-92 treatment, suggesting a regulatory role of ERK5 on Bcl2 phosphorylation...
December 6, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27878304/upregulation-of-mek5-by-stat3-promotes-breast-cancer-cell-invasion-and-metastasis
#2
Fang Liu, Hao Zhang, Hui Song
Mitogen extracellular-signal-regulated kinase kinase 5 (MEK5) plays an important role in promoting cell proliferation and tumorigenesis. The aberrant expression of MEK5 has been reported in various malignant diseases including cancers of breast, prostate, lung, colorectal and brain. However, the function and regulation of MEK5 signaling pathway are ambiguous and remain elusive with respect to its oncogenic roles in various cancers, especially in the regulation of the initiation and progression of cancer invasion and metastasis...
November 18, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27851987/evaluation-of-inflammation-related-signaling-events-covering-phosphorylation-and-nuclear-translocation-of-proteins-based-on-mass-spectrometry-data
#3
Andrea Bileck, Rupert L Mayer, Dominique Kreutz, Tamara Weiss, Sabine Taschner-Mandl, Samuel M Meier, Astrid Slany, Christopher Gerner
: Peripheral blood mononuclear cells are important players in immune regulation relying on a complex network of signaling pathways. In this study, we evaluated the power of label-free quantitative shotgun proteomics regarding the comprehensive characterization of signaling pathways in such primary cells by studying regulation of protein abundance, post-translational modifications and nuclear translocation events. The effects of inflammatory stimulation and the treatment of stimulated cells with dexamethasone were investigated...
November 13, 2016: Journal of Proteomics
https://www.readbyqxmd.com/read/27836247/implication-of-vhl-erk5-and-hif-1alpha-in-clear-cell-renal-cell-carcinoma-molecular-basis
#4
Leticia Serrano-Oviedo, José M Giménez-Bachs, Syongh Y Nam-Cha, Francisco J Cimas, Jesús García-Cano, Ricardo Sánchez-Prieto, Antonio S Salinas-Sánchez
OBJECTIVES: To determine the expression status of several proteins related to VHL gene function and its relationship with common clinicopathological parameters. MATERIAL AND METHODS: Observational, analytical, cross-sectional study with 50 patients diagnosed with clear cell renal cell carcinoma. The study analyzed VHL mutations and hypermethylation as well as protein expression of VHL, CA-IX, HIF-1alpha, VEGF, ERK1/2, and ERK5, relating them to clinical variables...
November 8, 2016: Urologic Oncology
https://www.readbyqxmd.com/read/27821723/c1q-tnf-related-protein-9-promotes-cardiac-hypertrophy-and-failure
#5
Mahesh Appari, Astrid Breitbart, Florian Brandes, Malgorzata Szaroszyk, Natali Froese, Mortimer Korf-Klingebiel, Mona Malek Mohammadi, Andrea Grund, Gesine M Scharf, Honghui Wang, Carolin Zwadlo, Daniela Fraccarollo, Ulrike Schrameck, Mona Nemer, William Wong, Hugo A Katus, Kai C Wollert, Oliver J Müller, Johann Bauersachs, Joerg Heineke
RATIONALE: Myocardial endothelial cells promote cardiomyocyte hypertrophy, possibly through the release of growth factors. The identity of these factors, however, remains largely unknown, and we hypothesized here that the secreted C1q-TNF-related protein-9 (CTRP9) might act as endothelial derived protein to modulate heart remodeling in response to pressure overload. OBJECTIVE: To examine the source of cardiac CTRP9 and its function during pressure overload. METHODS AND RESULTS: CTRP9 was mainly derived from myocardial capillary endothelial cells...
November 7, 2016: Circulation Research
https://www.readbyqxmd.com/read/27806338/mir-143-suppresses-the-epithelial-mesenchymal-transition-of-spinal-glioblastoma-through-down-regulation-of-erk5
#6
Yi Yan, Jing Wu, Mingjun Wu, Yongzhi Xia, Wenyuan Tang, Zhengbu Liao
The spinal glioblastoma (GBM) represents the one of most common tumors in humans. However, the biological processes and molecular mechanisms of spinal GBM are still unclear. It is known that miR-143 participates in the development of various tumor progressions. The present study was to evaluate the level of miR-143 in spinal GBM tissues and cells. We further investigated that the molecular mechanisms of miR-143 in U87 and U251 cell lines. Here, our data showed that the expression levels of miR-143 were significantly reduced in spinal GBM tissues and cell lines...
October 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27793024/absence-of-erk5-mapk7-delays-tumorigenesis-in-atm-mice
#7
Alba Granados-Jaén, Maria Angulo-Ibáñez, Xavier Rovira-Clavé, Celina Paola Vasquez Gamez, Francesc X Soriano, Manuel Reina, Enric Espel
Ataxia-telangiectasia mutated (ATM) is a cell cycle checkpoint kinase that upon activation by DNA damage leads to cell cycle arrest and DNA repair or apoptosis. The absence of Atm or the occurrence of loss-of-function mutations in Atm predisposes to tumorigenesis. MAPK7 has been implicated in numerous types of cancer with pro-survival and pro-growth roles in tumor cells, but its functional relation with tumor suppressors is not clear. In this study, we show that absence of MAPK7 delays death due to spontaneous tumor development in Atm-/- mice...
October 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27771897/profiling-of-signaling-proteins-in-penumbra-after-focal-photothrombotic-infarct-in-the-rat-brain-cortex
#8
Svetlana Demyanenko, Anatoly Uzdensky
In ischemic stroke, cell damage propagates from infarct core to surrounding tissue. To reveal proteins involved in neurodegeneration and neuroprotection, we explored the protein profile in penumbra surrounding the photothrombotic infarct core induced in rat cerebral cortex by local laser irradiation after Bengal Rose administration. Using antibody microarrays, we studied changes in expression of 224 signaling proteins 1, 4, or 24 h after photothrombotic infarct compared with untreated contralateral cortex...
October 22, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27748139/nuclear-erk5-inhibits-progression-of-leukemic-monocytes-to-macrophages-by-regulating-the-transcription-factor-pu-1-and-heat-shock-protein-hsp70
#9
Ruifang Zheng, George P Studzinski
Differentiation therapy can supplement the therapy of APL, but other subtypes of AML are treated principally with cytotoxic agents, with few lasting remissions. While the induction of monocyte followed by macrophage differentiation by vitamin D derivatives (VDDs) is dramatic in cultured AML cells of all subtypes, attempts to translate this to the clinic have not been effective. Thus, better understanding of the mechanisms underlying VDD-induced differentiation may improve this approach. The key events in this form of differentiation include increased expression of CD11b, and the transcription factor PU...
October 17, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27742373/scutellarin-attenuates-vasospasm-through-the-erk5-klf2-enos-pathway-after-subarachnoid-hemorrhage-in-rats
#10
Qiang Li, Yujie Chen, Xuan Zhang, Shilun Zuo, Hongfei Ge, Yanyan Chen, Xin Liu, John H Zhang, Huaizhen Ruan, Hua Feng
Angiographic vasospasm, especially in the early phases (<72h) of subarachnoid hemorrhage (SAH), is one of the major complications after an aneurysm rupture and is often the cause of delayed neurological deterioration. Scutellarin (SCU), a flavonoid extracted from the traditional Chinese herb Erigeron breviscapus, has been widely accepted as an antioxidant, but the effect of SCU on vasospasm after SAH remains elusive. Endovascular perforation was conducted to induce SAH in Sprague-Dawley rats. Then, the underlying mechanism of the anti-vasospasm effect of SCU was investigated using a modified Garcia scale, India ink angiography, cross-sectional area analysis, immunohistochemistry staining and western blot...
October 11, 2016: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/27735944/cdk5-functions-as-a-tumor-promoter-in-human-colorectal-cancer-via-modulating-the-erk5-ap-1-axis
#11
Kangmin Zhuang, Juchang Zhang, Man Xiong, Xianfei Wang, Xiaobei Luo, Lu Han, Yan Meng, Yali Zhang, Wenting Liao, Side Liu
Abnormal expression of cyclin-dependent kinase 5 (CDK5) has been found in several human cancers, whereas the role of CDK5 in the malignant development of colorectal cancer (CRC) has not been well characterized. Here we investigated the role of CDK5 in CRC and found that its expression was much higher in CRC tissues than that in normal tissues with a higher expression level of CDK5 closely correlating to advanced American Joint Committee on Cancer (AJCC) stage, poor differentiation, increased tumor size and poor prognosis of CRC...
October 13, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27717083/t-cell-acute-lymphoblastic-leukemia-in-infants-has-distinct-genetic-and-epigenetic-features-compared-to-childhood-cases
#12
Mareike Doerrenberg, Andreas Kloetgen, Kebria Hezaveh, Wilhelm Wössmann, Kirsten Bleckmann, Martin Stanulla, Martin Schrappe, Alice C McHardy, Arndt Borkhardt, Jessica I Hoell
For reasons not yet understood, nearly all infants with acute lymphoblastic leukemia (ALL) are diagnosed with the B-cell type, with T-ALL in infancy representing a very rare exception. Clinical and molecular knowledge about infant T-ALL is still nearly completely lacking and it is also still unclear whether it represents a distinct disease compared to childhood T-ALL. To address this, we performed exome sequencing of three infant cases, which enabled the detection of mutations in NOTCH2, NOTCH3, PTEN, and KRAS...
September 26, 2016: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/27713878/erk5-and-cell-proliferation-nuclear-localization-is-what-matters
#13
Nestor Gomez, Tatiana Erazo, Jose M Lizcano
ERK5, the last MAP kinase family member discovered, is activated by the upstream kinase MEK5 in response to growth factors and stress stimulation. MEK5-ERK5 pathway has been associated to different cellular processes, playing a crucial role in cell proliferation in normal and cancer cells by mechanisms that are both dependent and independent of its kinase activity. Thus, nuclear ERK5 activates transcription factors by either direct phosphorylation or acting as co-activator thanks to a unique transcriptional activation TAD domain located at its C-terminal tail...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27704743/research-progress-of-the-role-and-mechanism-of-extracellular-signal-regulated-protein-kinase-5-erk5-pathway-in-pathological-pain
#14
Li-Na Yu, Li-Hong Sun, Min Wang, Min Yan
Extracellular signal-regulated protein kinase 5 (ERK5), also known as big mitogen-activated protein kinase 1 (MAPK1), is an important member of ERK family, which is a subfamily of the large MAPK family. ERK5 is expressed in many tissues, including the dorsal root ganglion (DRG) neurons and the spinal cord. In this review, we focus on elaborating ERK5-associated pathway in pathological pain, in which the ERK5/CREB (cyclic adenosine monophosphate (cAMP)-response element-binding protein) pathway plays a crucial role in the transduction of pain signal and contributes to pain hypersensitivity...
2016: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/27698893/mir-143-is-associated-with-proliferation-and-apoptosis-involving-erk5-in-hela-cells
#15
Fang Zheng, Jiahe Zhang, Siyu Luo, Jing Yi, Ping Wang, Quanqing Zheng, Yurong Wen
Inappropriate expression of microRNA (miR) is strongly associated with carcinogenesis. miR-143 was reported to be one of the most prominent miRs implicated in the genesis and progression of human cancer. However, its correlation with cell proliferation and apoptosis in cervical cancer remains to be fully elucidated. In the present study, it was demonstrated that miR-143 is able to suppress the proliferation of cervical cancer HeLa cells and induce cell apoptosis in a time- and dose-dependent manner. The present study also investigated the potential targets of miR-143, extracellular-signal-regulated kinase 5 (ERK5) and its downstream substrate oncoprotein c-Fos, both of which are involved in cell proliferation and apoptosis...
October 2016: Oncology Letters
https://www.readbyqxmd.com/read/27679845/erk5-kinase-activity-is-dispensable-for-cellular-immune-response-and-proliferation
#16
Emme C K Lin, Christopher M Amantea, Tyzoon K Nomanbhoy, Helge Weissig, Junichi Ishiyama, Yi Hu, Shyama Sidique, Bei Li, John W Kozarich, Jonathan S Rosenblum
Unlike other members of the MAPK family, ERK5 contains a large C-terminal domain with transcriptional activation capability in addition to an N-terminal canonical kinase domain. Genetic deletion of ERK5 is embryonic lethal, and tissue-restricted deletions have profound effects on erythroid development, cardiac function, and neurogenesis. In addition, depletion of ERK5 is antiinflammatory and antitumorigenic. Small molecule inhibition of ERK5 has been shown to have promising activity in cell and animal models of inflammation and oncology...
October 18, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27660814/data-on-the-transcriptional-regulation-of-dna-damage-induced-apoptosis-suppressor-ddias-by-erk5-mef2b-pathway-in-lung-cancer-cells
#17
Joo-Young Im, Sung-Hoon Yoon, Bo-Kyung Kim, Hyun Seung Ban, Kyoung-Jae Won, Kyung-Sook Chung, Kyeong Eun Jung, Misun Won
The data included in this article are associated with the article entitled "DNA-damage-induced apoptosis suppressor (DDIAS) is upregulated via ERK5/MEF2B signaling and promotes β-catenin-mediated invasion" (J.Y. Im, S.H. Yoon, B.K. Kim, H.S. Ban, K.J. Won, K.S. Chung, K.E. Jung, M. Won) [1]. Quantitative RT-PCR data revealed that genetic or pharmacological inhibition of extracellular signal-regulated kinase 5 (ERK5) suppresses DDIAS transcription in response to epidermal growth factor (EGF) in Hela cells. p300 did not interact with myocyte enhancer factor 2B (MEF2B), a downstream target of ERK5 and affect transcription of DDIAS...
December 2016: Data in Brief
https://www.readbyqxmd.com/read/27606486/an-alternative-mode-of-cd43-signal-transduction-activates-pro-survival-pathways-of-t-lymphocytes
#18
Maria Elena Bravo-Adame, Rosario Vera-Estrella, Bronwyn J Barkla, Cecilia Martínez-Campos, Angel Flores-Alcantar, Jose Pablo Ocelotl-Oviedo, Gustavo Pedraza-Alva, Yvonne Rosenstein
CD43 is one of the most abundant co-stimulatory molecules on a T-cell surface; it transduces activation signals through its cytoplasmic domain, contributing to modulation of the outcome of T-cell responses. The aim of this study was to uncover new signalling pathways regulated by this sialomucin. Analysis of changes in protein abundance allowed us to identify pyruvate kinase isozyme M2 (PKM2), an enzyme of the glycolytic pathway, as an element potentially participating in the signalling cascade resulting from the engagement of CD43 and the T-cell receptor (TCR)...
January 2017: Immunology
https://www.readbyqxmd.com/read/27545608/microrna-200b-3p-suppresses-epithelial-mesenchymal-transition-and-inhibits-tumor-growth-of-glioma-through-down-regulation-of-erk5
#19
Jianguo Wu, Hongyan Cui, Zhifeng Zhu, Li Wang
Epithelial-mesenchymal transition (EMT) plays a pivotal role in the development of cancer. Has-miR-200b-3p is generally recognized as one of the fundamental regulators of EMT. In this study, we found that the expression of miR-200b-3p was downregulated in glioma tissues and human glioma cells U87 and U251. Meanwhile, Up-regulating miR-200b-3p enhanced E-cadherin, reduced mesenchymal markers, and decreased cell proliferation, migration, and invasion in vitro. In vivo, the xenograft mouse model also unveiled the suppressive effects of miR-200b-3p on tumor growth...
September 23, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27544204/mitogen-activated-protein-kinases-and-hypoxic-ischemic-nephropathy
#20
Fengbao Luo, Jian Shi, Qianqian Shi, Xianlin Xu, Ying Xia, Xiaozhou He
Tissue hypoxia/ischemia is a pathological feature of many human disorders including stroke, myocardial infarction, hypoxic/ischemic nephropathy, as well as cancer. In the kidney, the combination of limited oxygen supply to the tissues and high oxygen demand is considered the main reason for the susceptibility of the kidney to hypoxic/ischemic injury. In recent years, increasing evidence has indicated that a reduction in renal oxygen tension/blood supply plays an important role in acute kidney injury, chronic kidney disease, and renal tumorigenesis...
2016: Cellular Physiology and Biochemistry
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