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https://www.readbyqxmd.com/read/27913641/translation-repression-by-maternal-rna-binding-protein-zar1-is-essential-for-early-oogenesis-in-zebrafish
#1
Liyun Miao, Yue Yuan, Feng Cheng, Junshun Fang, Fang Zhou, Weirui Ma, Yan Jiang, Xiahe Huang, Yingchun Wang, Lingjuan Shan, Dahua Chen, Jian Zhang
Large numbers of maternal RNAs are deposited in oocytes and are reserved for later development. Control of maternal RNA translation during oocyte maturation has been extensively investigated and its regulatory mechanisms are well documented. However, translational regulation of maternal RNAs in early oogenesis is largely unexplored. In this study, we generated zebrafish zar1 mutants which result in early oocyte apoptosis and fully penetrant male development. Loss of p53 suppresses the apoptosis in zar1 mutants and restores oocyte development...
December 2, 2016: Development
https://www.readbyqxmd.com/read/27911860/id4-regulates-transcriptional-activity-of-wild-type-and-mutant-p53-via-k373-acetylation
#2
Derrick J Morton, Divya Patel, Jugal Joshi, Aisha Hunt, Ashley E Knowell, Jaideep Chaudhary
Given that mutated p53 (50% of all human cancers) is over-expressed in many cancers, restoration of mutant p53 to its wild type biological function has been sought after as cancer therapy. The conformational flexibility has allowed to restore the normal biological function of mutant p53 by short peptides and small molecule compounds. Recently, studies have focused on physiological mechanisms such as acetylation of lysine residues to rescue the wild type activity of mutant p53. Using p53 null prostate cancer cell line we show that ID4 dependent acetylation promotes mutant p53 DNA-binding capabilities to its wild type consensus sequence, thus regulating p53-dependent target genes leading to subsequent cell cycle arrest and apoptosis...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27907175/p53-specifically-binds-triplex-dna-in-vitro-and-in-cells
#3
Marie Brázdová, Vlastimil Tichý, Robert Helma, Pavla Bažantová, Alena Polášková, Aneta Krejčí, Marek Petr, Lucie Navrátilová, Olga Tichá, Karel Nejedlý, Martin L Bennink, Vinod Subramaniam, Zuzana Bábková, Tomáš Martínek, Matej Lexa, Matej Adámik
Triplex DNA is implicated in a wide range of biological activities, including regulation of gene expression and genomic instability leading to cancer. The tumor suppressor p53 is a central regulator of cell fate in response to different type of insults. Sequence and structure specific modes of DNA recognition are core attributes of the p53 protein. The focus of this work is the structure-specific binding of p53 to DNA containing triplex-forming sequences in vitro and in cells and the effect on p53-driven transcription...
2016: PloS One
https://www.readbyqxmd.com/read/27906185/anti-proliferative-activity-of-the-npm1-interacting-natural-product-avrainvillamide-in-acute-myeloid-leukemia
#4
Vibeke Andresen, Bjarte S Erikstein, Herschel Mukherjee, André Sulen, Mihaela Popa, Steinar Sørnes, Håkon Reikvam, Kok-Ping Chan, Randi Hovland, Emmet McCormack, Øystein Bruserud, Andrew G Myers, Bjørn T Gjertsen
Mutated nucleophosmin 1 (NPM1) acts as a proto-oncogene and is present in ~30% of patients with acute myeloid leukemia (AML). Here we examined the in vitro and in vivo anti-leukemic activity of the NPM1 and chromosome region maintenance 1 homolog (CRM1) interacting natural product avrainvillamide (AVA) and a fully syntetic AVA analog. The NPM1-mutated cell line OCI-AML3 and normal karyotype primary AML cells with NPM1 mutations were significantly more sensitive towards AVA than cells expressing wild-type (wt) NPM1...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27901050/the-use-of-the-nedd8-inhibitor-mln4924-pevonedistat-in-a-cyclotherapy-approach-to-protect-wild-type-p53-cells-from-mln4924-induced-toxicity
#5
Lara J Bou Malhab, Simon Descamps, Benedicte Delaval, Dimitris P Xirodimas
Targetting the ubiquitin pathway is an attractive strategy for cancer therapy. The inhibitor of the ubiquitin-like molecule NEDD8 pathway, MLN4924 (Pevonedistat) is in Phase II clinical trials. Protection of healthy cells from the induced toxicity of the treatment while preserving anticancer efficacy is a highly anticipated outcome in chemotherapy. Cyclotherapy was proposed as a promising approach to achieve this goal. We found that cytostatic activation of p53 protects cells against MLN4924-induced toxicity and importantly the effects are reversible...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27899992/beside-p53-and-pten-identification-of-molecular-alterations-of-the-ras-mapk-and-pi3k-akt-signaling-pathways-in-high-grade-serous-ovarian-carcinomas-to-determine-potential-novel-therapeutic-targets
#6
Shuhui Chen, Elisa Cavazza, Catherine Barlier, Julia Salleron, Pierre Filhine-Tresarrieu, Céline Gavoilles, Jean-Louis Merlin, Alexandre Harlé
Despite great histological and molecular heterogeneity, the clinical management of high-grade ovarian carcinomas remains unspecialized. As a major subgroup, high-grade serous ovarian carcinomas (HGSOCs) require novel therapies. In addition to utilizing conventional histological prognostic markers and performing oncogenetic investigations, the molecular diagnostic method of next generation sequencing (NGS) was performed to identify 'druggable' targets that could provide access to innovative therapy. The present study was performed in 45 HGSOC patients (mean age, 59...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899973/expression-patterns-of-maspin-and-mutant-p53-are-associated-with-the-development-of-gestational-trophoblastic-neoplasia
#7
Pengming Sun, Qibin Wu, Guanyu Ruan, Xiu Zheng, Yiyi Song, Jianfan Zhun, Lixiang Wu, Walter H Gotlieb
Gestational trophoblastic disease (GTD) is a group of conditions that originate from the abnormal proliferation of trophoblastic cells. GTDs encompass hydatidiform moles (HMs) and gestational trophoblastic neoplasia (GTN). GTNs are a group of malignant diseases that require chemotherapy, or more aggressive treatment. There is a requirement for more tumor markers to predict the development of GTN from HMs. The current study evaluated the expression of maspin and tumor protein p53 (p53) in GTD, and their role in predicting the development of GTN...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899647/spliceosomal-protein-eftud2-mutation-leads-to-p53-dependent-apoptosis-in-zebrafish-neural-progenitors
#8
Lei Lei, Shou-Yu Yan, Ran Yang, Jia-Yu Chen, Yumei Li, Ye Bu, Nannan Chang, Qinchao Zhou, Xiaojun Zhu, Chuan-Yun Li, Jing-Wei Xiong
Haploinsufficiency of EFTUD2 (Elongation Factor Tu GTP Binding Domain Containing 2) is linked to human mandibulofacial dysostosis, Guion-Almeida type (MFDGA), but the underlying cellular and molecular mechanisms remain to be addressed. We report here the isolation, cloning and functional analysis of the mutated eftud2 (snu114) in a novel neuronal mutant fn10a in zebrafish. This mutant displayed abnormal brain development with evident neuronal apoptosis while the development of other organs appeared less affected...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899303/gambogic-acid-counteracts-mutant-p53-stability-by-inducing-autophagy
#9
Giorgia Foggetti, Laura Ottaggio, Debora Russo, Paola Monti, Paolo Degan, Gilberto Fronza, Paola Menichini
Mutant p53 (mutp53) proteins are frequently present at higher levels than the wild-type (wt) protein in tumors, and some of them can acquire oncogenic properties. Consistently, knockdown of mutp53 protein in human cancer cell lines leads to reduced cell proliferation and invasion as well as to an increased sensitivity to some anticancer drugs. Therefore, the exploitation of cellular pathways and/or molecules that promote mutp53 degradation may have a therapeutic interest. Recently, autophagy is emerging as an important pathway involved in the stability of mutp53...
November 26, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27898034/emerging-non-canonical-functions-and-regulation-by-p53-p53-and-stemness
#10
REVIEW
David J Olivos, Lindsey D Mayo
Since its discovery nearly 40 years ago, p53 has ascended to the forefront of investigated genes and proteins across diverse research disciplines and is recognized most exclusively for its role in cancer as a tumor suppressor. Levine and Oren (2009) reviewed the evolution of p53 detailing the significant discoveries of each decade since its first report in 1979. In this review, we will highlight the emerging non-canonical functions and regulation of p53 in stem cells. We will focus on general themes shared among p53's functions in non-malignant stem cells and cancer stem-like cells (CSCs) and the influence of p53 on the microenvironment and CSC niche...
November 26, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27890807/diosmin-induced-senescence-apoptosis-and-autophagy-in-breast-cancer-cells-of-different-p53-status-and-erk-activity
#11
Anna Lewinska, Jagoda Adamczyk-Grochala, Ewa Kwasniewicz, Anna Deregowska, Maciej Wnuk
Relatively low bioavailability of plant-derived nutraceuticals with anticancer properties may limit their usefulness for prevention and therapy of cancer. In the present study, we have screened for nutraceuticals (n=30) that would act at low micromolar range against phenotypically distinct breast cancer cell lines, namely MCF-7 (ER(+), PR(+/-), HER2(-)), MDA-MB-231 (ER(-), PR(-), HER2(-)) and SK-BR-3 (ER(-), PR(-), HER2(+)), and diosmin, a citrus fruit flavonoid belonging to a flavone subclass, was selected...
November 24, 2016: Toxicology Letters
https://www.readbyqxmd.com/read/27886181/a-redox-mechanism-underlying-nucleolar-stress-sensing-by-nucleophosmin
#12
Kai Yang, Ming Wang, Yuzheng Zhao, Xuxu Sun, Yi Yang, Xie Li, Aiwu Zhou, Huilin Chu, Hu Zhou, Jianrong Xu, Mian Wu, Jie Yang, Jing Yi
The nucleolus has been recently described as a stress sensor. The nucleoplasmic translocation of nucleolar protein nucleophosmin (NPM1) is a hallmark of nucleolar stress; however, the causes of this translocation and its connection to p53 activation are unclear. Using single live-cell imaging and the redox biosensors, we demonstrate that nucleolar oxidation is a general response to various cellular stresses. During nucleolar oxidation, NPM1 undergoes S-glutathionylation on cysteine 275, which triggers the dissociation of NPM1 from nucleolar nucleic acids...
November 25, 2016: Nature Communications
https://www.readbyqxmd.com/read/27885271/p53-pathway-dysfunction-is-highly-prevalent-in-acute-myeloid-leukemia-independent-of-tp53-mutational-status
#13
A Quintás-Cardama, C Hu, A Qutub, Y H Qiu, X Zhang, S Post, N Zhang, K Coombes, S M Kornblau
TP53 mutations are associated with the lowest survival rates in acute myeloid leukemia (AML). In addition to mutations, loss of p53 function can arise via aberrant expression of proteins that regulate p53 stability and function. We examined a large AML cohort using proteomics, mutational profiling, and network analyses and showed that 1) p53 stabilization is universal in mutant TP53 samples, it is frequent in samples with wild-type TP53, and in both cases portends an equally dismal prognosis; 2) the p53 negative regulator Mdm2 is frequently overexpressed in samples retaining wild-type TP53 alleles, coupled with absence of p21 expression and dismal prognosis similar to that of cases with p53 stabilization; 3) AML samples display unique patterns of p53 pathway protein expression, which segregate prognostic groups with distinct cure rates; 4) such patterns of protein activation unveil potential AML vulnerabilities that can be therapeutically exploited...
November 25, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27878984/sulforaphane-induced-apoptosis-in-xuanwei-lung-adenocarcinoma-cell-line-xwlc-05
#14
Lan Zhou, Qian Yao, Yan Li, Yun-Chao Huang, Hua Jiang, Chuan-Qiong Wang, Lei Fan
BACKGROUND: Xuanwei district in Yunnan Province has the highest incidence of lung cancer in China, especially among non-smoking women. Cruciferous vegetables can reduce lung cancer risk by prompting a protective mechanism against respiratory tract inflammation caused by air pollution, and are rich in sulforaphane, which can induce changes in gene expression. We investigated the effect of sulforaphane-induced apoptosis in Xuanwei lung adenocarcinoma cell line (XWCL-05) to explore the value of sulforaphane in lung cancer prevention and treatment...
November 23, 2016: Thoracic Cancer
https://www.readbyqxmd.com/read/27878254/restoration-of-the-tumor-suppressor-function-to-mutant-p53-by-ganoderma-lucidum-polysaccharides-in-colorectal-cancer-cells
#15
Dan Jiang, Lingyao Wang, Tong Zhao, Zhaoyu Zhang, Renxia Zhang, Jingji Jin, Yong Cai, Fei Wang
Ganoderma lucidum polysaccharides (GLPs), isolated from spores, mycelia and fruiting bodies of Ganoderma lucidum, have been suggested to possess anticancer activities in a large number of basic studies. A recent survey revealed that GLP-induced inhibition of cancer cell growth was dependent on the existence of functional p53. However, the actual role of p53-mediated tumor-suppressing pathways in facilitating the anticancer effect of GLPs is still unclear. In the present study, we investigated the interaction between GLPs and mutant p53 that exists in more than half of the known types of cancers...
November 15, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27873457/using-yeast-to-determine-the-functional-consequences-of-mutations-in-the-human-p53-tumor-suppressor-gene-an-introductory-course-based-undergraduate-research-experience-in-molecular-and-cell-biology
#16
Daria S Hekmat-Scafe, Sara E Brownell, Patricia Chandler Seawell, Shyamala Malladi, Jamie F Conklin Imam, Veena Singla, Nicole Bradon, Martha S Cyert, Tim Stearns
The opportunity to engage in scientific research is an important, but often neglected, component of undergraduate training in biology. We describe the curriculum for an innovative, course-based undergraduate research experience (CURE) appropriate for a large, introductory cell and molecular biology laboratory class that leverages students' high level of interest in cancer. The course is highly collaborative and emphasizes the analysis and interpretation of original scientific data. During the course, students work in teams to characterize a collection of mutations in the human p53 tumor suppressor gene via expression and analysis in yeast...
November 22, 2016: Biochemistry and Molecular Biology Education
https://www.readbyqxmd.com/read/27872090/mutational-landscape-of-pediatric-acute-lymphoblastic-leukemia
#17
LingWen Ding, Qiao-Yang Sun, Kar-Tong Tan, Wenwen Chien, Anand Mayakonda Thippeswamy, Allen Yeoh Eng Juh, Norihiko Kawamata, Yasunobu Nagata, Jin-Fen Xiao, Xin-Yi Loh, De-Chen Lin, Manoj Garg, Su-Lin Lim, Li-Zhen Liu, Vikas Madan, Yan-Yi Jiang, Liang Xu, Masashi Sanada, Lucia Torres Fernández, Hema Preethi, Michael Lill, Hagop Kantarjian, S M Kornblau, Satoru Miyano, Seishi Ogawa, Der-Cherng Liang, Lee-Yung Shih, Henry Yang, H Phillip Koeffler
Current standard of care for patients with pediatric acute lymphoblastic leukemia (ALL) is mainly effective, with high remission rates after treatment. However, the genetic perturbations that give rise to this disease remain largely undefined, limiting the ability to address resistant tumors or develop less toxic targeted therapies. Here we report the use of next generation sequencing to interrogate the genetic and pathogenic mechanisms of 240 pediatric ALL cases with their matched remission samples. Commonly mutated genes fell into several categories, including RAS/receptor tyrosine kinases, epigenetic regulators, transcription factors involved in lineage commitment and the p53/cell cycle pathway...
November 21, 2016: Cancer Research
https://www.readbyqxmd.com/read/27871965/molecular-interplay-between-mutant-p53-proteins-and-autophagy-in-cancer-cells
#18
REVIEW
Marco Cordani, Giovanna Butera, Raffaella Pacchiana, Massimo Donadelli
An increasing number of studies highlight the role of mutant p53 proteins in cancer cell growth and in the worsening of cancer patients' clinical outcome. Autophagy has been widely recognized as a main biological event involved in both the regulation of cancer cell proliferation and in the response of several anticancer drugs. A thorough analysis of scientific literature underlines the reciprocal interplay between mutant p53 proteins and autophagy regulation. In this review, we analytically summarize recent findings, which indicate that gain-of-function (GOF) mutant p53 proteins counteract the autophagic machinery by various molecular mechanisms including the regulation of AMPK and Akt/mTOR pathways, autophagy-related genes (ATGs), HIF-1α target genes, and the mitochondrial citrate carrier CIC...
November 19, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27871934/v-src-induced-nuclear-localization-of-yap-is-involved-in-multipolar-spindle-formation-in-tetraploid-cells
#19
Keiko Kakae, Masayoshi Ikeuchi, Takahisa Kuga, Youhei Saito, Naoto Yamaguchi, Yuji Nakayama
The protein-tyrosine kinase, c-Src, is involved in a variety of signaling events, including cell division. We have reported that v-Src, which is a mutant variant of the cellular proto-oncogene, c-Src, causes delocalization of Aurora B kinase, resulting in a furrow regression in cytokinesis and the generation of multinucleated cells. However, the effect of v-Src on mitotic spindle formation is unknown. Here we show that v-Src-expressing HCT116 and NIH3T3 cells undergo abnormal cell division, in which cells separate into more than two cells...
November 18, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27869650/inhibiting-mitochondrial-respiration-prevents-cancer-in-a-mouse-model-of-li-fraumeni-syndrome
#20
Ping-Yuan Wang, Jie Li, Farzana L Walcott, Ju-Gyeong Kang, Matthew F Starost, S Lalith Talagala, Jie Zhuang, Ji-Hoon Park, Rebecca D Huffstutler, Christina M Bryla, Phuong L Mai, Michael Pollak, Christina M Annunziata, Sharon A Savage, Antonio Tito Fojo, Paul M Hwang
Li-Fraumeni syndrome (LFS) is a cancer predisposition disorder caused by germline mutations in TP53 that can lead to increased mitochondrial metabolism in patients. However, the implications of altered mitochondrial function for tumorigenesis in LFS are unclear. Here, we have reported that genetic or pharmacologic disruption of mitochondrial respiration improves cancer-free survival in a mouse model of LFS that expresses mutant p53. Mechanistically, inhibition of mitochondrial function increased autophagy and decreased the aberrant proliferation signaling caused by mutant p53...
November 21, 2016: Journal of Clinical Investigation
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