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https://www.readbyqxmd.com/read/28417973/excitability-in-the-p53-network-mediates-robust-signaling-with-tunable-activation-thresholds-in-single-cells
#1
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
#2
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
#3
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...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28385459/wip1-a-candidate-phosphatase-for-cancer-diagnosis-and-treatment
#4
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...
March 20, 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
#5
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
#6
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)...
February 14, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28185954/wip1-directly-dephosphorylates-nlk-and-increases-wnt-activity-during-germ-cell-development
#7
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
#8
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...
February 8, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28144241/phosphatase-wip1-in-immunity-an-overview-and-update
#9
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
#10
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
#11
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...
January 17, 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
#12
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
https://www.readbyqxmd.com/read/27991505/wip1-inhibitor-gsk2830371-inhibits-neuroblastoma-growth-by-inducing-chk2-p53-mediated-apoptosis
#13
Zhenghu Chen, Long Wang, Dayong Yao, Tianshu Yang, Wen-Ming Cao, Jun Dou, Jonathan C Pang, Shan Guan, Huiyuan Zhang, Yang Yu, Yanling Zhao, Yongfeng Wang, Xin Xu, Yan Shi, Roma Patel, Hong Zhang, Sanjeev A Vasudevan, Shangfeng Liu, Jianhua Yang, Jed G Nuchtern
Neuroblastoma (NB) is the most common extracranial tumor in children. Unlike in most adult tumors, tumor suppressor protein 53 (p53) mutations occur with a relatively low frequency in NB and the downstream function of p53 is intact in NB cell lines. Wip1 is a negative regulator of p53 and hindrance of Wip1 activity by novel inhibitor GSK2830371 is a potential strategy to activate p53's tumor suppressing function in NB. Yet, the in vivo efficacy and the possible mechanisms of GSK2830371 in NB have not yet been elucidated...
December 19, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27959454/clinical-significance-of-wip1-overexpression-and-its-association-with-the-p38mapk-p53-p16-pathway-in-nsclc
#14
Shize Yang, Siyuan Dong, Xiaohan Qu, Xinwen Zhong, Qigang Zhang
Wip1 is deregulated in numerous human malignancies. However, its roles in non‑small cell lung cancer (NSCLC) remain unclear. In the current study, the expression of Wip1 was investigated in NSCLC and its clinical significance was detected. Immunohistochemical staining was used to measure the expression of (wild‑type p53 induced phosphatase 1) Wip1, p38 mitogen‑activated protein kinase (MAPK), p53, p16 protein in a group of 60 NSCLC and 20 normal lung tissues. In addition, western blotting was performed to detect the Wip1 protein in fresh tissues...
February 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27713908/ppm1d-wip1-in-medulloblastoma
#15
EDITORIAL
Mwangala P Akamandisa, Rita Nahta, Robert C Castellino
No abstract text is available yet for this article.
2016: Oncoscience
https://www.readbyqxmd.com/read/27687530/wip-1-inhibits-intestinal-inflammation-in-inflammatory-bowel-disease
#16
Qi Zhang, Cuiping Zhang, Fangzhi Chang, Kun Liang, Xiaoyan Yin, Xiaoyu Li, Kun Zhao, Qinghui Niu, Zibin Tian
Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a chronically intestinal autoimmune disease, the pathological mechanisms of which are not very clear. Wild type p-53 induced phosphatase 1 (Wip1), a serine/threonine protein phosphatase, has been reported to negatively regulate the inflammation in sepsis. However, the role of Wip1 in IBD is not very clear. Therefore, colonic tissues and peripheral blood from patients with IBD and healthy controls were collected to analyzed mRNA and protein expression of Wip1 using the method of qPCR and immunohistochemistry...
July 25, 2016: Cellular Immunology
https://www.readbyqxmd.com/read/27686532/gamma-h2ax-upregulation-caused-by-wip1-deficiency-increases-depression-related-cellular-senescence-in-hippocampus
#17
Zhi-Yong He, Wen-Yue Wang, Wei-Yan Hu, Lu Yang, Yan Li, Wei-Yuan Zhang, Ya-Shu Yang, Si-Cheng Liu, Feng-Lan Zhang, Rong Mei, Da Xing, Zhi-Cheng Xiao, Ming Zhang
The PP2C family member Wild-type p53-induced phosphatase 1 (Wip1) critically regulates DNA damage response (DDR) under stressful situations. In the present study, we investigated whether Wip1 expression was involved in the regulation of DDR-induced and depression-related cellular senescence in mouse hippocampus. We found that Wip1 gene knockout (KO) mice showed aberrant elevation of hippocampal cellular senescence and of γ-H2AX activity, which is known as a biomarker of DDR and cellular senescence, indicating that the lack of Wip1-mediated γ-H2AX dephosphorylation facilitates cellular senescence in hippocampus...
September 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27526774/a-novel-mathematical-model-of-atm-p53-nf-%C3%AE%C2%BAb-pathways-points-to-the-importance-of-the-ddr-switch-off-mechanisms
#18
Katarzyna Jonak, Monika Kurpas, Katarzyna Szoltysek, Patryk Janus, Agata Abramowicz, Krzysztof Puszynski
BACKGROUND: Ataxia telangiectasia mutated (ATM) is a detector of double-strand breaks (DSBs) and a crucial component of the DNA damage response (DDR) along with p53 and NF- κB transcription factors and Wip1 phosphatase. Despite the recent advances in studying the DDR, the mechanisms of cell fate determination after DNA damage induction is still poorly understood. RESULTS: To investigate the importance of various DDR elements with particular emphasis on Wip1, we developed a novel mathematical model of ATM/p53/NF- κB pathways...
August 15, 2016: BMC Systems Biology
https://www.readbyqxmd.com/read/27524485/ccan-assembly-configures-composite-binding-interfaces-to-promote-cross-linking-of-ndc80-complexes-at-the-kinetochore
#19
Gülsah Pekgöz Altunkaya, Francesca Malvezzi, Zuzana Demianova, Tomasz Zimniak, Gabriele Litos, Florian Weissmann, Karl Mechtler, Franz Herzog, Stefan Westermann
Partitioning of the genome requires kinetochores, large protein complexes that mediate dynamic attachment of chromosomes to the spindle. Kinetochores contain two supramolecular protein assemblies. The ten-protein KMN network harbors key microtubule-binding sites in the Ndc80 complex and mediates assembly of checkpoint complexes via the KNL-1/Spc105 protein [1, 2]. As KMN does not contact DNA directly, it relies on different centromere-binding proteins for recruitment and cell-cycle-dependent assembly. These proteins are collectively referred to as the CCAN (constitutive centromere-associated network) [2-4]...
September 12, 2016: Current Biology: CB
https://www.readbyqxmd.com/read/27505679/wip1-controls-global-heterochromatin-silencing-via-atm-brca1-dependent-dna-methylation
#20
Doria Filipponi, Julius Muller, Alexander Emelyanov, Dmitry V Bulavin
No abstract text is available yet for this article.
August 8, 2016: Cancer Cell
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