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https://www.readbyqxmd.com/read/28780681/interaction-of-wip1-and-nf-%C3%AE%C2%BAb-regulates-neuroinflammatory-response-in-astrocytes
#1
Fan Xu, Lifei Chen, Xin Zhao, Haibin Zhong, Ling Cui, Li Jiang, Hui Huang, Li Li, Siming Zeng, Min Li
OBJECTIVE: The aims of the present study were to detect the interaction of Wip1 and NF-κB P65 in retina of an LPS-induced astrocytes activation model. METHODS: The interaction between Wip1 and nuclear factor kappa B (NF-κB) P65 was observed in lipopolysaccharide (LPS)-stimulated primary rat astrocytes derived from retina. The expressions of Wip1 and NF-κB P65 were evaluated using Western blot and RT-PCR. Small interfering RNA (siRNA) against Wip1 was transfected into astrocytes to clarify the phosphorylation status and nuclear translocation of NF-κB P65 and expressions of these proinflammatory factors...
August 5, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28732646/phosphatase-wip1-controls-the-development-of-th9-cells-and-allergic-airway-inflammation
#2
Peng Wang, Huiting Su, Lianjun Zhang, Hui Chen, Xuelian Hu, Fan Yang, Jun Lu, Lianfeng Zhang, Yong Zhao
BACKGROUND: Allergic asthma is one of the most common diseases worldwide, resulting in a burden of diseases. No available therapeutic regimens can cure asthma so far. OBJECTIVE: To identify new molecular targets for Th9 cells-mediated allergic airway inflammation. METHODS: Wild-type p53-induced phosphatase 1 (Wip1) gene knockout mice, Wip1 inhibitor-treated mice and ovalbumin (OVA)-induced allergic airway inflammation mouse models were employed to characterize the roles of Wip1 in allergic airway inflammation...
July 18, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28654910/microrna16-regulates-glioma-cell-proliferation-apoptosis-and-invasion-by-targeting-wip1-atm-p53-feedback-loop
#3
Xiao-Hong Zhan, Qiu-Yan Xu, Rui Tian, Hong Yan, Min Zhang, Jing Wu, Wei Wang, Jie He
The present study aimed to investigate the role and underlying mechanisms of microRNA16 (miR-16) on proliferation, apoptosis and invasion of glioma cells. The cell models of miR-16 upregulation and Negative control group (NC group) were built. The cell functions of different groups were detected by colony formation assay, transwell chamber assay, proliferation, apoptosis and cycle experiments. The intracranial orthotopic transplantation animal models were built to different groups: miR-16 agomir group, miR-16 antagomir group and their NC group...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28607002/atm-wip1-activities-at-chromatin-control-plk1-re-activation-to-determine-g2-checkpoint-duration
#4
Himjyot Jaiswal, Jan Benada, Erik Müllers, Karen Akopyan, Kamila Burdova, Tobias Koolmeister, Thomas Helleday, René H Medema, Libor Macurek, Arne Lindqvist
After DNA damage, the cell cycle is arrested to avoid propagation of mutations. Arrest in G2 phase is initiated by ATM-/ATR-dependent signaling that inhibits mitosis-promoting kinases such as Plk1. At the same time, Plk1 can counteract ATR-dependent signaling and is required for eventual resumption of the cell cycle. However, what determines when Plk1 activity can resume remains unclear. Here, we use FRET-based reporters to show that a global spread of ATM activity on chromatin and phosphorylation of ATM targets including KAP1 control Plk1 re-activation...
July 14, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28599292/wip1-is-associated-with-tumorigenity-and-metastasis-through-mmp-2-in-human-intrahepatic-cholangiocarcinoma
#5
Sulai Liu, Bo Jiang, Hao Li, Zili He, Pin Lv, Chuang Peng, Yonggang Wang, Wei Cheng, Zhengquan Xu, Wei Chen, Zhengkai Liu, Bao Zhang, Shengqian Shen, Shuanglin Xiang
Wip1 has been shown to correlate with the metastasis/invasion of several tumors. This study was designed to investigate the clinical significance and biological function of Wip1 in intrahepatic cholangiocarcinoma (ICC). The expression of Wip1 was investigated in sixty human ICC biopsy samples by immunohistochemistry. Transient and stable knockdown of Wip1 in two human ICC cells (ICC-9810 and SSP25) were established using short hairpin RNA expression vector. Immunohistochemistry revealed that Wip1 was up-regulated in human ICC tissues (47/60, 78...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28524834/wild-type-p53-induced-phosphatase-1-deficiency-exacerbates-myocardial-infarction-induced-ischemic-injury
#6
Ke-Mei Liu, Hai-Hong Zhang, Ya-Nan Wang, Lian-Mei Wang, Hong-Yu Chen, Cai-Feng Long, Lian-Feng Zhang, Hong-Bing Zhang, Hong-Bing Yan
BACKGROUND: Myocardial infarction (MI) is a major disease burden. Wild-type p53-induced phosphatase 1 (Wip1) has been studied extensively in the context of cancer and the regulation of different types of stem cells, but the role of Wip1 in cardiac adaptation to MI is unknown. We investigated the significance of Wip1 in a mouse model of MI. METHODS: The study began in June 2014 and was completed in July 2016. We compared Wip1-knockout (Wip1-KO) mice and wild-type (WT) mice to determine changes in cardiac function and survival in response to MI...
June 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28440479/wip1-regulates-skov3-cell-apoptosis-through-the-p38-mapk-signaling-pathway
#7
Yanping Feng, Fang Liu, Zhixiang Du, Dongjie Zhao, Jianxin Cheng, Wei Guo
The aim of the present study was to explore the effect of silencing wild‑type p53‑induced phosphatase 1 (Wip1) on apoptosis of human ovarian cancer SKOV3 cells. SKOV3 cells cultured in vitro were divided into three groups: untreated cells, cells transfected with control small interfering RNA (siRNA) and cells transfected with siRNA targeting Wip1. Flow cytometry analysis was used to detect cell apoptosis. Western blot analysis was performed to determine expression of tumor protein 53 (p53), cleaved caspase‑3, caspase‑3, BCL2 associated X (Bax), BCL2 apoptosis regulator (Bcl‑2), p38 mitogen‑activated protein kinase (p38 MAPK) and phosphorylated (p)‑p38 MAPK...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28439615/wip1-phosphatase-as-pharmacological-target-in-cancer-therapy
#8
REVIEW
Soňa Pecháčková, Kamila Burdová, Libor Macurek
DNA damage response (DDR) pathway protects cells from genome instability and prevents cancer development. Tumor suppressor p53 is a key molecule that interconnects DDR, cell cycle checkpoints, and cell fate decisions in the presence of genotoxic stress. Inactivating mutations in TP53 and other genes implicated in DDR potentiate cancer development and also influence the sensitivity of cancer cells to treatment. Protein phosphatase 2C delta (referred to as WIP1) is a negative regulator of DDR and has been proposed as potential pharmaceutical target...
June 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28417973/excitability-in-the-p53-network-mediates-robust-signaling-with-tunable-activation-thresholds-in-single-cells
#9
Gregor Mönke, Elena Cristiano, Ana Finzel, Dhana Friedrich, Hanspeter Herzel, Martin Falcke, Alexander Loewer
Cellular signaling systems precisely transmit information in the presence of molecular noise while retaining flexibility to accommodate the needs of individual cells. To understand design principles underlying such versatile signaling, we analyzed the response of the tumor suppressor p53 to varying levels of DNA damage in hundreds of individual cells and observed a switch between distinct signaling modes characterized by isolated pulses and sustained oscillations of p53 accumulation. Guided by dynamic systems theory we show that this requires an excitable network structure comprising positive feedback and provide experimental evidence for its molecular identity...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28417018/dna-damage-induced-phosphatase-wip1-in-regulation-of-hematopoiesis-immune-system-and-inflammation
#10
REVIEW
B Uyanik, B B Grigorash, A R Goloudina, O N Demidov
PP2C serine-threonine phosphatase, Wip1, is an important regulator of stress response. Wip1 controls a number of critical cellular functions: proliferation, cell cycle arrest, senescence and programmed cell death, apoptosis or autophagy. Ppm1d, the gene encoding Wip1 phosphatase, is expressed in hematopoietic progenitors, stem cells, neutrophils, macrophages B and T lymphocytes in bone marrow and peripheral blood. The Wip1-/- mice display immunodeficiency, abnormal lymphoid histopathology in thymus and spleen, defects in B- and T-cell differentiation, as well as susceptibility to viral infection...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28402943/expression-of-wild-type-p53-induced-phosphatase-1-in-diabetic-epiretinal-membranes
#11
Jiping Xu, Haibin Zhong, Ling Cui, Qianqian Lan, Lifei Chen, Wenjing He, Yu Wu, Li Jiang, Hui Huang, Xin Zhao, Li Li, Siming Zeng, Min Li, Fan Xu
OBJECTIVE: The aims of the present study were to investigate the expression and distribution of Wild-type p53-induced phosphatase 1 (Wip1) in diabetic patients with proliferative diabetic retinopathy (PDR) with epiretinal membranes (ERMs) meanwhile analyze the colocalization of Wip1 and nuclear factor kappa-B (NF-κB) p65 in ERMs. METHODS: ERMs samples were collected from patients with PDR (PDR group) or non-diabetic patients with idiopathic epiretinal membranes (iERMs) (control group) during pars plana vitrectomy...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28385459/wip1-a-candidate-phosphatase-for-cancer-diagnosis-and-treatment
#12
REVIEW
Tayebeh Oghabi Bakhshaiesh, Keivan Majidzadeh-A, Rezvan Esmaeili
The critical regulatory mechanisms in numerous cellular pathways including cell survival and DNA damage response mostly depend on phosphorylation and dephosphorylation of proteins. The serine/threonine phosphatase wild-type p53-induced phosphatase 1 (Wip1) is a growth-promoting phosphatase and its numerous downstream targets are important tumor suppressors. Here, we review the Wip1 activity and its relevance to cancer as an oncoprotein. Consecutive investigations about Wip1 and its relation to cancer is critical, as these studies ultimately contribute to the etiology of cancer...
June 2017: DNA Repair
https://www.readbyqxmd.com/read/28356972/wild-type-p53-induced-phosphatase-1-is-a-prognostic-marker-and-therapeutic-target-in-bladder-transitional-cell-carcinoma
#13
Zhi-Peng Wang, Shu-Yuan Chen, Ye Tian
Wild-type p53-induced phosphatase (Wip1) is an established oncogene and is associated with development of multiple forms of human cancer. However, the expression and role of Wip1 in human bladder transitional cell carcinoma (TCC) remains to be elucidated. In the present study, immunohistochemistry demonstrated that Wip1 was overexpressed in bladder TCC tissues compared with corresponding normal bladder tissues in 106 bladder TCC cases (P<0.0001). Furthermore, high expression levels of Wip1 were significantly associated with increasing tumor size (P=0...
February 2017: Oncology Letters
https://www.readbyqxmd.com/read/28195382/contribution-of-atm-and-atr-kinase-pathways-to-p53-mediated-response-in-etoposide-and-methyl-methanesulfonate-induced-dna-damage
#14
Bin Sun, Susan M Ross, Sean Rowley, Yeyejide Adeleye, Rebecca A Clewell
p53 is a key integrator of cellular response to DNA damage, supporting post-translational repair and driving transcription-mediated responses including cell cycle arrest, apoptosis, and repair. DNA damage sensing kinases recognize different types of DNA damage and initiate specific responses through various post-translational modifications of p53. This study evaluated chemical specificity of the p53 pathway response by manipulating p53 or its upstream kinases and assessing the effect on DNA damage and cellular responses to prototype chemicals: etoposide (ETP, topoisomerase II inhibitor) and methyl methane sulfonate (MMS, alkylating agent)...
March 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28185954/wip1-directly-dephosphorylates-nlk-and-increases-wnt-activity-during-germ-cell-development
#15
Seung-Ju Cho, Bok-Sik Cha, Ok-Seon Kwon, Jisun Lim, Dong-Myung Shin, Dong Wook Han, Tohru Ishitani, Eek-Hoon Jho, Albert J Fornace, Hyuk-Jin Cha
Mice null for wild-type p53-induced phosphatase 1 (WIP1) display defects in testis development and spermatogenesis, resulting in reduced fertility. However, the molecular mechanism underlying these abnormalities in the testis remains uncharacterized. We report that the phosphatase activity of WIP1 increases Wnt activity through Nemo-like kinase (NLK). WIP1 directly interacted with NLK, which is highly homologous to p38 MAPK, a WIP1 substrate, and dephosphorylated its activation site. The WIP1-mediated inhibition of NLK activity markedly decreased the phosphorylation of lymphoid enhancer-binding factor 1 (LEF1), enhancing its interaction with β-catenin...
April 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28180926/wip1-phosphatase-is-a-critical-regulator-of-adipogenesis-through-dephosphorylating-ppar%C3%AE-serine-112
#16
Dahu Li, Lijun Zhang, Lun Xu, Lili Liu, Yunling He, Yiyao Zhang, Xin Huang, Tong Zhao, Liying Wu, Yongqi Zhao, Kuiwu Wu, Hui Li, Xiao Yu, Taiyun Zhao, Shenghui Gong, Ming Fan, Lingling Zhu
WIP1, as a critical phosphatase, plays many important roles in various physiological and pathological processes through dephosphorylating different substrate proteins. However, the functions of WIP1 in adipogenesis and fat accumulation are not clear. Here, we report that WIP1-deficient mice show impaired body weight growth, dramatically decreased fat mass, and significantly reduced triglyceride and leptin levels in circulation. This dysregulation of adipose development caused by the deletion of WIP1 occurs as early as adipogenesis...
June 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28144241/phosphatase-wip1-in-immunity-an-overview-and-update
#17
REVIEW
Xiao-Fei Shen, Yang Zhao, Jin-Peng Jiang, Wen-Xian Guan, Jun-Feng Du
Wild-type p53-induced phosphatase 1 (Wip1) is a newly identified serine/threonine phosphatase, which belongs to the PP2C family. Due to its involvement in stress-induced networks and overexpression in human tumors, primary studies have mainly focused on the role of Wip1 in tumorigenesis. It now has also been implicated in regulating several other physiological processes such as organism aging and neurogenesis. Recent evidence highlights a new role of Wip1 in controlling immune response through regulating immune cell development and function, as well as through the interplay with inflammatory signaling pathways such NF-κB and p38 mitogen-activated protein kinase...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28105167/cisplatin-induces-hepg2-cell-cycle-arrest-through-targeting-specific-long-noncoding-rnas-and-the-p53-signaling-pathway
#18
Ping Wang, Jiayue Cui, Jihong Wen, Yunhui Guo, Liangzi Zhang, Xia Chen
Cisplatin has been used effectively in the treatment of hepatocellular carcinoma (HCC). Long noncoding RNAs (lncRNAs) were recently reported to contribute to the pathogenesis and progression of HCC. Their molecular mechanism related to cisplatin treatment remains unclear. The purpose of this study is to identify specific lncRNAs and to clarify their functions in HCC after cisplatin exposure. Reannotation and identification of differentially expressed lncRNAs were performed using the microarray data set GSE38122 in the Gene Expression Omnibus database...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28097612/wip1-phosphatase-plays-a-critical-neuroprotective-role-in-brain-injury-induced-by-high-altitude-hypoxic-inflammation
#19
Dahu Li, Lijun Zhang, Xin Huang, Lili Liu, Yunling He, Lun Xu, Yiyao Zhang, Tong Zhao, Liying Wu, Yongqi Zhao, Kuiwu Wu, Yan Wu, Ming Fan, Lingling Zhu
The hypobaric hypoxic environment in high-altitude areas often aggravates the severity of inflammation and induces brain injury as a consequence. However, the critical genes regulating this process remain largely unknown. The phosphatase wild-type p53-induced phosphatase 1 (WIP1) plays important roles in various physiological and pathological processes, including the regulation of inflammation in normoxia, but its functions in hypoxic inflammation-induced brain injury remain unclear. Here, we established a mouse model of this type of injury and found that WIP1 deficiency augmented the release of inflammatory cytokines in the peripheral circulation and brain tissue, increased the numbers of activated microglia/macrophages in the brain, aggravated cerebral histological lesions, and exacerbated the impairment of motor and cognitive abilities...
June 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28027003/lzap-is-a-novel-wip1-binding-partner-and-positive-regulator-of-its-phosphatase-activity-in-vitro
#20
J Jacob Wamsley, Natalia Issaeva, Hanbing An, Xinyuan Lu, Lawrence A Donehower, Wendell G Yarbrough
The phosphatase Wip1 attenuates the DNA damage response (DDR) by removing phosphorylation marks from a number of DDR proteins (p53, MDM2, Chk1/2, p38). Wip1 also dephosphorylates and inactivates RelA. Notably, LZAP, a putative tumor suppressor, has been linked to dephosphorylation of several of these substrates, including RelA, p38, Chk1, and Chk2. LZAP has no known catalytic activity or functional motifs, suggesting that it exerts its effects through interaction with other proteins. Here we show that LZAP binds Wip1 and stimulates its phosphatase activity...
January 17, 2017: Cell Cycle
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