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p53 mdm2

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https://www.readbyqxmd.com/read/28549433/js-k-a-nitric-oxide-pro-drug-regulates-growth-and-apoptosis-through-the-ubiquitin-proteasome-pathway-in-prostate-cancer-cells
#1
Guobin Tan, Mingning Qiu, Lieqian Chen, Sai Zhang, Longzhi Ke, Jianjun Liu
BACKGROUND: In view of the fact that JS-K might regulate ubiquitin E3 ligase and that ubiquitin E3 ligase plays an important role in the mechanism of CRPC formation, the goal was to investigate the probable mechanism by which JS-K regulates prostate cancer cells. METHODS: Proliferation inhibition by JS-K on prostate cancer cells was examined usingCCK-8 assays. Caspase 3/7 activity assays and flow cytometry were performed to examine whether JS-K induced apoptosis in prostate cancer cells...
May 26, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28544069/cd38-enhances-the-proliferation-and-inhibits-the-apoptosis-of-cervical-cancer-cells-by-affecting-the-mitochondria-functions
#2
Shan Liao, Songshu Xiao, Hongxiang Chen, Manying Zhang, Zhifang Chen, Yuehua Long, Lu Gao, Guangchao Zhu, Junyu He, Shuping Peng, Wei Xiong, Zhaoyang Zeng, Zheng Li, Ming Zhou, Xiaoling Li, Jian Ma, Minghua Wu, Juanjuan Xiang, Guiyuan Li, Yanhong Zhou
Cervical cancer is one of the most common malignant tumors in women all over the world. The exact mechanism of occurrence and development of cervical cancer has not been fully elucidated. CD38 is a type II transmembrane glycoprotein, which was found to mediate diverse activities, including signal transduction, cell adhesion, and cyclic ADP-ribose synthesis. Here, we reported that CD38 promoted cell proliferation and inhibited cell apoptosis in cervical cancer cells by affecting the mitochondria functions. We established stable cervical cancer cell lines with CD38 over-expressed...
May 23, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28542136/pak4-regulates-g6pd-activity-by-p53-degradation-involving-colon-cancer-cell-growth
#3
Xiumei Zhang, Xia Zhang, Yang Li, Yangguang Shao, Jianying Xiao, Ge Zhu, Feng Li
The p21-activated kinase 4 (PAK4) is overexpressed in different cancers and promotes proliferation of cancer cells. Reprogramming of glucose metabolism is found in most cancer cells which in turn supports rapid proliferation. However, the relationship between PAK4 and glucose metabolism in cancer cells has not been explored. In this study, we reported that PAK4 promoted glucose intake, NADPH production and lipid biosynthesis, leading to an increased proliferation of colon cancer cells. Mechanistically, PAK4 interacted with glucose-6-phosphate dehydrogenase (G6PD), a rate-limiting enzyme of the pentose phosphate pathway and increased G6PD activity via enhancing Mdm2-mediated p53 ubiquitination degradation...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28539160/phosphorylation-of-p53-at-threonine-155-is-required-for-jab1-mediated-nuclear-export-of-p53
#4
Eun-Woo Lee, Wonkyung Oh, Hosung Paul Song, Won Kon Kim
The Jun activation-domain binding protein 1 (Jab1) induces p53 nuclear export and cytoplasmic degradation. However, the underlying mechanism is not clearly addressed. Here, we identify that phosphorylation at threonine 155 residue is indispensable for Jab1-mediated p53 nuclear export. Jab1 stimulated phosphorylation of p53 at T155, which was inhibited by curcumin, an inhibitor of COP9 signalosome (CSN)-associated kinases. T155E mutant, which mimics phosphorylated p53, exhibited spontaneous cytoplasmic localization in the absence of Jab1...
May 25, 2017: BMB Reports
https://www.readbyqxmd.com/read/28535015/the-circadian-clock-gene-per2-plays-an-important-role-in-tumor-suppression-through-regulating-tumor-associated-genes-in-human-oral-squamous-cell-carcinoma
#5
Xiaoli Su, Dan Chen, Kai Yang, Qin Zhao, Dan Zhao, Xiaoqiang Lv, Yiran Ao
Low expression of the clock gene PER2 is closely related to carcinogenesis and the development of cancer; however, the mechanism of the low expression of PER2 that led to cell malignant transformation remains unclear. This study used RNA interference (RNAi) technology to silence PER2 in SCC15 human oral squamous cell carcinoma (OSCC) cells. Then it was found that the ability of cancer cell proliferation, migration, and invasion were markedly increased (P<0.05), and the ability of cancer cell apoptosis and the number of cells in G1/G0 phase were markedly reduced (P<0...
May 19, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28533414/manipulating-dna-damage-response-signaling-for-the-treatment-of-immune-mediated-diseases
#6
Jonathan P McNally, Scott H Millen, Vandana Chaturvedi, Nora Lakes, Catherine E Terrell, Eileen E Elfers, Kaitlin R Carroll, Simon P Hogan, Paul R Andreassen, Julie Kanter, Carl E Allen, Michael M Henry, Jay N Greenberg, Stephan Ladisch, Michelle L Hermiston, Michael Joyce, David A Hildeman, Jonathan D Katz, Michael B Jordan
Antigen-activated lymphocytes undergo extraordinarily rapid cell division in the course of immune responses. We hypothesized that this unique aspect of lymphocyte biology leads to unusual genomic stress in recently antigen-activated lymphocytes and that targeted manipulation of DNA damage-response (DDR) signaling pathways would allow for selective therapeutic targeting of pathological T cells in disease contexts. Consistent with these hypotheses, we found that activated mouse and human T cells display a pronounced DDR in vitro and in vivo...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28511869/markers-of-the-p53-pathway-further-refine-molecular-profiling-in-high-risk-endometrial-cancer-a-transportec-initiative
#7
R J Edmondson, E J Crosbie, M Nickkho-Amiry, A Kaufmann, E Stelloo, H W Nijman, A Leary, A Auguste, L Mileshkin, P Pollock, H J MacKay, M E Powell, T Bosse, C L Creutzberg, H C Kitchener
BACKGROUND: The morphological classification of high-risk endometrial cancer is of limited prognostic value. Recent attempts to stratify tumours according to molecular signatures have shown considerable promise. Here we attempted to further refine molecular classifications using markers of the p53 pathway. METHODS: We analysed the expression of p53 as well as three downstream markers of the p53 pathway, p21, mdm2 and phospho-p63 (pp63), by immunohistochemistry in a series of 114 endometrial cancers (86 endometrioid, 28 non-endometrioid subtype) with high-risk features (such as high tumour grade and deep myometrial invasion) and correlated results with clinical outcome...
May 13, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28507478/melatonin-regulates-the-aging-mouse-hippocampal-homeostasis-via-the-sirtuin1-foxo1-pathway
#8
Anorut Jenwitheesuk, Parichart Boontem, Prapimpun Wongchitrat, Jiraporn Tocharus, Sujira Mukda, Piyarat Govitrapong
Sirtuin1 (SIRT1) and forkhead box transcription factor O subfamily 1 (FOXO1) play vital roles in the maintenance of hippocampal neuronal homeostasis during aging. Our previous study showed that melatonin, a hormone mainly secreted by the pineal gland, restored the impaired memory of aged mice. Age-related neuronal energy deficits contribute to the pathogenesis of several neurodegenerative disorders. An attempt has been made to determine whether the effect of melatonin is mediated through the SIRT1-FOXO1 pathways...
2017: EXCLI journal
https://www.readbyqxmd.com/read/28499267/a-novel-germline-tp53-mutation-p-pro190arg-detected-in-a-patient-with-lung-and-bilateral-breast-cancers
#9
Małgorzata Krześniak, Dorota Butkiewicz, Jadwiga Rachtan, Iwona Matuszczyk, Ewa Grzybowska, Marek Rusin
PURPOSE: Li-Fraumeni syndrome (LFS) is a rare genetic disease with strong predispositions to multiple early-onset neoplasms, mostly sarcomas, breast cancers, brain tumors and adrenocortical carcinomas (LFS core cancers). In most LFS families the germline mutations of TP53 tumor suppressor gene were found. Lung cancer does not belong to the core cancers of LFS, however its higher incidence is observed in families with TP53 mutations. Our aim was to search for TP53 mutations in female lung cancer patients whose clinico-demographic characteristics suggested a probable genetic predisposition to the disease...
May 9, 2017: Advances in Medical Sciences
https://www.readbyqxmd.com/read/28498808/restoration-of-p53-using-the-novel-mdm2-p53-antagonist-apg115-suppresses-dedifferentiated-papillary-thyroid-cancer-cells
#10
Haibo Chen, Dingyuan Luo, Lin Zhang, Xiaofeng Lin, Qiuyun Luo, Hanjie Yi, Jing Wang, Xianglei Yan, Baoxia Li, Yuelei Chen, Xingguang Liu, Hong Zhang, Sheng Liu, Miaozhen Qiu, Dajun Yang, Ningyi Jiang
Dedifferentiated papillary thyroid cancer (DePTC) is characterized by aggressive growth, recurrence, distant metastasis, and resistance to radioactive iodine (RAI) therapy. DePTC is also accompanied by poor prognosis and high early-mortality. Nevertheless, most DePTC cells show intact p53 downstream functionality. In cells with wild-type p53, the murine double minute2 (MDM2) protein interacts with p53 and abrogates its activity. Inhibition of the MDM2-p53 interaction restores p53 activity and leads to cell cycle arrest and apoptosis...
April 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28496125/enhancing-specific-disruption-of-intracellular-protein-complexes-by-hydrocarbon-stapled-peptides-using-lipid-based-delivery
#11
D Thean, J S Ebo, T Luxton, Xue'Er Cheryl Lee, T Y Yuen, F J Ferrer, C W Johannes, D P Lane, C J Brown
Linear peptides can mimic and disrupt protein-protein interactions involved in critical cell signaling pathways. Such peptides however are usually protease sensitive and unable to engage with intracellular targets due to lack of membrane permeability. Peptide stapling has been proposed to circumvent these limitations but recent data has suggested that this method does not universally solve the problem of cell entry and can lead to molecules with off target cell lytic properties. To address these issues a library of stapled peptides was synthesized and screened to identify compounds that bound Mdm2 and activated cellular p53...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28484902/the-molecular-mechanisms-of-protective-role-of-se-on-the-g2-m-phase-arrest-of-jejunum-caused-by-afb1
#12
Jing Fang, Heng Yin, Zhixiang Zheng, Panpan Zhu, Xi Peng, Zhicai Zuo, Hengmin Cui, Yi Zhou, Ping Ouyang, Yi Geng, Junliang Deng
Aflatoxin B1 (AFB1) is the most toxic among the mycotoxins and causes detrimental health effects on human and animals. Selenium (Se) plays an important role in chemopreventive, antioxidant, anticarcinogen, and detoxification and involved in cell cycle regulation. The aim of this study was to explore the molecular mechanisms of selenium involved in inhibition of G2/M cell cycle arrest of broiler's jejunum. A total of 240 one-day-old healthy Cobb broilers were randomly divided into four groups and fed with basal diet (control group), 0...
May 9, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28484602/ppimpred-a-web-server-for-high-throughput-screening-of-small-molecules-targeting-protein-protein-interaction
#13
Tanmoy Jana, Abhirupa Ghosh, Sukhen Das Mandal, Raja Banerjee, Sudipto Saha
PPIMpred is a web server that allows high-throughput screening of small molecules for targeting specific protein-protein interactions, namely Mdm2/P53, Bcl2/Bak and c-Myc/Max. Three different kernels of support vector machine (SVM), namely, linear, polynomial and radial basis function (RBF), and two other machine learning techniques including Naive Bayes and Random Forest were used to train the models. A fivefold cross-validation technique was used to measure the performance of these classifiers. The RBF kernel of SVM outperformed and/or was comparable with all other methods with accuracy values of 83%, 79% and 90% for Mdm2/P53, Bcl2/Bak and c-Myc/Max, respectively...
April 2017: Royal Society Open Science
https://www.readbyqxmd.com/read/28483982/akt3-is-responsible-for-the-survival-and-proliferation-of-embryonic-stem-cells
#14
Ling Wang, Delun Huang, Zongliang Jiang, Yan Luo, Carol Norris, Ming Zhang, Xiuchun Tian, Young Tang
The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/Akt) pathway plays an important role in regulating cell proliferation, metabolism, and survival. However, the distinct roles of Akt isoforms - Akt1, Akt2, and Akt3 in pluripotent stem cell maintenance are not fully defined. Using mouse embryonic stem cells (ESCs), we show that direct inhibition of Akt activity leads to ESC apoptosis. The Akt3, but not Akt1 or Akt2 activity specifically regulates this effect. Inhibiting Akt3 also leads to a cell cycle arrest at G1 phase...
May 8, 2017: Biology Open
https://www.readbyqxmd.com/read/28482147/1-4-5-trisubstituted-imidazole-based-p53-mdm2-mdmx-antagonists-with-aliphatic-linkers-for-conjugation-with-biological-carriers
#15
Aleksandra Twarda-Clapa, Sylwia Krzanik, Katarzyna Kubica, Katarzyna Guzik, Beata Labuzek, Constantinos G Neochoritis, Kareem Khoury, Kaja Kowalska, Miroslawa Czub, Grzegorz Dubin, Alexander Dömling, Lukasz Skalniak, Tad A Holak
The tumor suppressor protein p53, the "guardian of the genome", is inactivated in nearly all cancer types by mutations in the TP53 gene or by overexpression of its negative regulators, oncoproteins MDM2/MDMX. Recovery of p53 function by disrupting the p53-MDM2/MDMX interaction using small-molecule antagonists could provide an efficient nongenotoxic anticancer therapy. Here we present the syntheses, activities, and crystal structures of the p53-MDM2/MDMX inhibitors based on the 1,4,5-trisubstituted imidazole scaffold which are appended with aliphatic linkers that enable coupling to bioactive carriers...
May 16, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28477272/hif-1%C3%AE-mdm2-cdk4-and-p16-expression-in-ischemic-fasciitis-focusing-on-its-ischemic-condition
#16
Yuichi Yamada, Izumi Kinoshita, Kenichi Kohashi, Hidetaka Yamamoto, Yuki Kuma, Takamichi Ito, Kenji Koda, Atsushi Kisanuki, Manabu Kurosawa, Michiko Yoshimura, Masutaka Furue, Yoshinao Oda
Ischemic fasciitis is a benign myofibroblastic lesion, occurring in the sacral region or proximal thigh of elderly or bedridden individuals. The pathogenesis of ischemic fasciitis is thought to be based on ischemic condition; however, it has never been demonstrated. In this study, we examined the expression of ischemia-associated proteins in ischemic fasciitis by immunohistochemical and genetic methods. Specifically, this study aimed to reveal the expression of HIF-1α, MDM2, CDK4, p16, and gene amplification of MDM2 gene...
May 6, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28477117/studies-of-atm-kinase-activity-using-engineered-atm-sensitive-to-atp-analogues-atm-as
#17
Masato Enari, Yuko Matsushima-Hibiya, Makoto Miyazaki, Ryo Otomo
Ataxia-telangiectasia mutated (ATM) protein is a member of the phosphatidylinositol 3-phosphate kinase (PI3-K)-related protein kinase (PIKK) family and is implicated in the initiation of signaling pathways following DNA double strand breaks (DSBs) elicited by exposure to ionizing irradiation (IR) or radiomimetic compounds. Loss of function of the ATM gene product results in the human genetic disorder ataxia-telangiectasia (A-T) characterized by neurodegeneration, immunodeficiency, genomic instability, and cancer predisposition...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28468838/hiv-1-tat-potently-stabilizes-mdm2-and-enhances-viral-replication
#18
Rameez Raja, Larance Ronsard, Sneh Lata, Shubhendu Trivedi, Akhil C Banerjea
Murine double minute 2 (Mdm2) is known to enhance the transactivation potential of human immunodeficiency virus (HIV-1) Tat protein by ubiquitinating it. However, the regulation of Mdm2 during HIV-1 infection and its implications on viral replication have not been well studied. Here, we show that the Mdm2 protein level increases during HIV-1 infection and this effect is mediated by HIV-1 Tat protein. Tat appears to stabilise Mdm2 at the post-translational level by inducing its phosphorylation at serine-166 position through AKT...
May 3, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28460439/tumorigenesis-promotes-mdm4-s-overexpression
#19
Vinod Pant, Connie A Larsson, Neeraj Aryal, Shunbin Xiong, M James You, Alfonso Quintas-Cardama, Guillermina Lozano
Disruption of the p53 tumor suppressor pathway is a primary cause of tumorigenesis. In addition to mutation of the p53 gene itself, overexpression of major negative regulators of p53, MDM2 and MDM4, also act as drivers for tumor development. Recent studies suggest that expression of splice variants of Mdm2 and Mdm4 may be similarly involved in tumor development. In particular, multiple studies show that expression of a splice variant of MDM4, MDM4-S correlates with tumor aggressiveness and can be used as a prognostic marker in different tumor types...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28454566/apoptosis-induced-effects-of-extract-from-artemisia-annua-linn%C3%A3-by-modulating-pten-p53-pdk1-akt-signal-pathways-through-pten-p53-independent-manner-in-hct116-colon-cancer-cells
#20
Eun Ji Kim, Guen Tae Kim, Bo Min Kim, Eun Gyeong Lim, Sang-Yong Kim, Young Min Kim
BACKGROUND: The extracts from Artemisia annua Linné (AAE) has been known to possess various functions including anti-bacterial, anti-virus and anti-oxidant effects. However, the mechanism of those effects of AAE is not well known. Pursuantly, we determined the apoptotic effects of extract of AAE in HCT116 cell. In this study, we suggested that AAE may exert cancer cell apoptosis through PTEN/PDK1/Akt/p53signal pathway and mitochondria-mediated apoptotic proteins. METHODS: We measured 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) assay, Hoechst 33342 staining, Annexin V-PI staining, Mitopotential assay, immunofluorescence (IF) and Western blotting...
April 28, 2017: BMC Complementary and Alternative Medicine
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