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https://www.readbyqxmd.com/read/29733326/wip1-phosphatase-suppresses-the-dna-damage-response-during-g2-prophase-arrest-in-mouse-oocytes
#1
Jiyeon Leem, Jae-Sung Kim, Jeong Su Oh
Maternal DNA damage during meiosis causes genetic abnormalities that can lead to infertility, birth defects, and abortion. While DNA damage can rapidly halt cell cycle progression and promote DNA repair in somatic cells, mammalian oocytes are unable to mount a robust G2/prophase arrest in response to DNA damage unless damage levels are severe. Here we show that inhibition of WIP1 phosphatase enhances the ability of oocytes to respond to DNA damage. We found that WIP1 was expressed constantly during meiotic maturation, and that inhibition of WIP1 activity did not impair meiotic maturation...
May 3, 2018: Biology of Reproduction
https://www.readbyqxmd.com/read/29476592/chemical-features-important-for-activity-in-a-class-of-inhibitors-targeting-the-wip1-flap-subdomain
#2
Harichandra D Tagad, Subrata Debnath, Victor Clausse, Mrinmoy Saha, Sharlyn J Mazur, Ettore Appella, Daniel H Appella
The wild-type p53 induced phosphatase 1, Wip1 (PP2Cδ), is a protein phosphatase 2C (PP2C) family serine/threonine phosphatase that negatively regulates the function of the tumor suppressor p53 and several of its positive regulators such as ATM, Chk1, Chk2, Mdm2, and p38 MAPK. Wip1 dephosphorylates and inactivates its protein targets, which are critical for cellular stress responses. Additionally, Wip1 is frequently amplified and overexpressed in several human cancer types. Because of its negative role in regulating the function of tumor suppressor proteins, Wip1 has been identified as a potential therapeutic target in various types of cancers...
May 8, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29367109/nf-%C3%AE%C2%BAb-induced-wip1-expression-promotes-colorectal-cancer-cell-proliferation-through-mtor-signaling
#3
Fei Bai, Huijun Zhou, Zhongping Fu, Jiangbo Xie, Yingbin Hu, Shaolin Nie
Colorectal cancer (CRC) is one of the major causes of cancer deaths worldwide. Wild-type p53-induced protein 1 (WIP1) is overexpressed in multiple human cancers and acted as an oncogene. This study was aimed to investigate the effect of WIP1 in colorectal cancer growth and analyzed underlying mechanisms. Herein, we determined WIP1 expression in CRC tissues and cell lines, as well as evaluated its detailed function in CRC cell proliferation. Several factors have been reported to mediate WIP1 effects; herein, we examined the involvement of mTOR and p21 in WIP1 regulation of CRC cell proliferation...
March 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29343567/parainfluenza-virus-infection-sensitizes-cancer-cells-to-dna-damaging-agents-implications-for-oncolytic-virus-therapy
#4
Candace R Fox, Griffith D Parks
We have previously shown that the Parainfluenza virus 5 (PIV5) mutant P/V-CPI- is restricted for spread in normal cells but not in cancer cells in vitro and is effective at reducing tumor burden in mouse model systems. Here we show that P/V-CPI- infection of human laryngeal cancer HEp-2 cells results in the majority of the cells dying, but unexpectedly, over time there is an emergence of a population of cells which survive as P/V-CPI- persistently infected (PI) cells. P/V-CPI- PI cells had elevated levels of basal caspase activation, and viability was highly dependent on activity of cellular inhibitors of apoptosis (IAPs) such as Survivin and XIAP...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29337287/revealing-determinants-of-two-phase-dynamics-of-p53-network-under-gamma-irradiation-based-on-a-reduced-2d-relaxation-oscillator-model
#5
Gökhan Demirkıran, Güleser Kalaycı Demir, Cüneyt Güzeliş
This study proposes a two-dimensional (2D) oscillator model of p53 network, which is derived via reducing the multidimensional two-phase dynamics model into a model of ataxia telangiectasia mutated (ATM) and Wip1 variables, and studies the impact of p53-regulators on cell fate decision. First, the authors identify a 6D core oscillator module, then reduce this module into a 2D oscillator model while preserving the qualitative behaviours. The introduced 2D model is shown to be an excitable relaxation oscillator...
February 2018: IET Systems Biology
https://www.readbyqxmd.com/read/29275106/clinical-significance-of-the-wild-type-p53-induced-phosphatase-1-expression-in-invasive-breast-cancer
#6
Yuka Inoue, Nami Yamashita, Hiroyuki Kitao, Kimihiro Tanaka, Hiroshi Saeki, Eiji Oki, Yoshinao Oda, Eriko Tokunaga, Yoshihiko Maehara
BACKGROUND: Wild type p53-induced phosphatase 1 (Wip1), encoded by the protein phosphatase magnesium dependent 1 delta (PPM1D), inhibits p53. PPM1D amplification has been reported in breast cancer. Breast cancer can sometimes develop without a tumor protein 53 (TP53) mutation. In these cases, the p53 pathway might be disrupted by alternative mechanisms, and Wip1 is reported to be a key molecule involved. MATERIALS AND METHODS: Primary invasive ductal carcinoma specimens were obtained from 201 cases, for which archival tissue samples for immunohistochemistry were available...
November 21, 2017: Clinical Breast Cancer
https://www.readbyqxmd.com/read/29235570/targeting-negative-regulation-of-p53-by-mdm2-and-wip1-as-a-therapeutic-strategy-in-cutaneous-melanoma
#7
Chiao-En Wu, Arman Esfandiari, Yi-Hsuan Ho, Nan Wang, Ahmed Khairallah Mahdi, Erhan Aptullahoglu, Penny Lovat, John Lunec
BACKGROUND: Cutaneous melanoma is the most serious skin malignancy and new therapeutic strategies are needed for advanced melanoma. TP53 mutations are rare in cutaneous melanoma and hence activation of wild-type p53 is a potential therapeutic strategy in cutaneous melanoma. Here, we investigated the WIP1 inhibitor, GSK2830371, and MDM2-p53 binding antagonists (nutlin-3, RG7388 and HDM201) alone and in combination treatment in cutaneous melanoma cell lines and explored the mechanistic basis of these responses in relation to the genotype and induced gene expression profile of the cells...
February 20, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29128669/wip1-regulates-blood-brain-barrier-function-and-neuro-inflammation-induced-by-lipopolysaccharide-via-the-sonic-hedgehog-signaling-signaling-pathway
#8
Hong Zhen, Lize Zhao, Zhangjun Ling, Li Kuo, Xiarui Xue, Jiaxiu Feng
The blood brain barrier (BBB) is a diffusion barrier that maintains the brain environment. Wip1 is a nuclear phosphatase induced by many factors and involved in various stresses, tumorigenesis, organismal aging, and neurogenesis. Wip1's role in BBB integrity has not been thoroughly investigated. The purpose of the present study was to investigate the effect and mechanism of Wip1 on lipopolysaccharide (LPS)-induced BBB dysfunction and inflammation in an in vitro BBB model. The in vitro BBB model was established by co-culturing human brain-microvascular endothelial cells and human astrocytes and then exposing them to 1μg/ml LPS for 6, 12, 18, 24, and 48h...
January 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29039507/effect-of-the-adenovirus%C3%A2-mediated-wip1-gene-on-lumbar-intervertebral-disc-degeneration-in-a-rabbit-model
#9
Yuan Wang, Yong Yang, Jing-Chuan Sun, Qin-Jie Kong, Hai-Bo Wang, Jian-Gang Shi
The present study aimed to investigate the effect of the adenovirus‑mediated wild‑type p53‑induced protein phosphatase 1 (Wip1) gene on lumbar disc degeneration (LDD) in a rabbit model. Adult New Zealand white rabbits were used as experimental subjects. The rabbits were divided into LDD groups (groups A‑C of rabbit models of LDD) and control groups (groups D‑F of normal rabbits). The animals in groups A and D were injected with the Wip1 gene vector, those in groups B and E were injected with an empty vector, and those in groups C and F were injected with phosphate‑buffered saline...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28968438/microrna-16-feedback-loop-with-p53-and-wip1-can-regulate-cell-fate-determination-between-apoptosis-and-senescence-in-dna-damage-response
#10
Maria Vitória C Issler, José Carlos M Mombach
Cell fate regulation is an open problem whose comprehension impacts several areas of the biosciences. DNA damage induces cell cycle checkpoints that activate the p53 pathway to regulate cell fate mechanisms such as apoptosis or senescence. Experiments with different cell types show that the p53 pathway regulates cell fate through a switch behavior in its dynamics. For low DNA damage the pathway presents an oscillatory pattern associated with intense DNA damage repair while for high damage there are no oscillations and either p53 concentration increases inducing apoptosis or the cell enters a senescence state...
2017: PloS One
https://www.readbyqxmd.com/read/28959360/role-of-wild-type-p53-induced-phosphatase-1-in-cancer
#11
Zhi-Peng Wang, Ye Tian, Jun Lin
Wild-type p53-induced phosphatase (Wip1) is a member of the protein phosphatase type 2C family and is an established oncogene due to its dephosphorylation of several tumor suppressors and negative control of the DNA damage response system. It has been reported to dephosphorylate p53, ataxia telangiectasia mutated, checkpoint kinase 1 and p38 mitogen activated protein kinases, forming negative feedback loops to inhibit apoptosis and cell cycle arrest. Wip1 serves a major role in tumorigenesis, progression, invasion, distant metastasis and apoptosis in various types of human cancer...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28915621/wip1-is-associated-with-tumorigenity-and-metastasis-through-mmp-2-in-human-intrahepatic-cholangiocarcinoma
#12
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...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903382/microrna16-regulates-glioma-cell-proliferation-apoptosis-and-invasion-by-targeting-wip1-atm-p53-feedback-loop
#13
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...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28878779/wip1-deficiency-promotes-neutrophil-recruitment-to-the-infection-site-and-improves-sepsis-outcome
#14
Xiao-Fei Shen, Yang Zhao, Ke Cao, Wen-Xian Guan, Xue Li, Qian Zhang, Yong Zhao, Yi-Tao Ding, Jun-Feng Du
Sepsis is defined as an uncontrolled host response to infection, and no specific therapy or drugs have been used in clinical trials currently. Discovering new therapeutic targets for sepsis treatment has always been a central problem in the field of sepsis research. Neutrophils stand at the first line in controlling infection and have been identified to be dysregulated with impaired migration and antimicrobial function during sepsis. Based on our previous results on demonstrating wild-type p53-induced phosphatase 1 in controlling neutrophil development, we explored the possible relationship among Wip1, neutrophils, and sepsis in the present study...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28822916/wip1-dependent-modulation-of-macrophage-migration-and-phagocytosis
#15
Yiting Tang, Bing Pan, Xin Zhou, Kai Xiong, Qian Gao, Lei Huang, Ying Xia, Ming Shen, Shulin Yang, Honglin Liu, Tao Tan, Jianjie Ma, Xuehong Xu, Yulian Mu, Kui Li
Macrophage accumulation within the vascular wall is a hallmark of atherosclerosis. Controlling macrophage conversion into foam cells remains a major challenge for treatment of atherosclerotic diseases. Here, we show that Wip1, a member of the PP2C family of Ser/Thr protein phosphatases, modulates macrophage migration and phagocytosis associated with atherosclerotic plaque formation. Wip1 deficiency increases migratory and phagocytic activities of the macrophage under stress conditions. Enhanced migration of Wip1(-/-) macrophages is mediated by Rac1-GTPase and PI3K/AKT signalling pathways...
August 12, 2017: Redox Biology
https://www.readbyqxmd.com/read/28780681/interaction-of-wip1-and-nf-%C3%AE%C2%BAb-regulates-neuroinflammatory-response-in-astrocytes
#16
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...
November 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
#17
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
#18
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
#19
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
#20
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
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