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P53 -apoptosis

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https://www.readbyqxmd.com/read/28813011/insights-into-the-effect-of-the-g245s-single-point-mutation-on-the-structure-of-p53-and-the-binding-of-the-protein-to-dna
#1
Marco Gaetano Lepre, Sara Ibrahim Omar, Gianvito Grasso, Umberto Morbiducci, Marco Agostino Deriu, Jack A Tuszynski
The transcription factor p53 is a potent tumor suppressor dubbed as the "guardian of the genome" because of its ability to orchestrate protective biological outputs in response to a variety of oncogenic stresses. Mutation and thus inactivation of p53 can be found in 50% of human tumors. The majority are missense mutations located in the DNA binding region. Among them, G245S is known to be a structural hotspot mutation. To understand the behaviors and differences between the wild-type and mutant, both a dimer of the wild type p53 (wt-p53) and its G245S mutant (G245S-mp53), complexed with DNA, were simulated using molecular dynamics for more than 1 μs...
August 16, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28811972/uncovering-the-immunotherapeutic-cycle-initiated-by-p19arf-and-interferon-%C3%AE-gene-transfer-to-cancer-cells-an-inducer-of-immunogenic-cell-death
#2
REVIEW
Ruan F V Medrano, Aline Hunger, João P P Catani, Bryan E Strauss
Simultaneous reestablishment of p53/p19(Arf) and interferon-β pathways in melanoma cells culminates in a cell death process that displays features of necroptosis along with the release of immunogenic cell death molecules and unleashes an antitumor immune response mediated by natural killer cells, neutrophils as well as CD4(+) and CD8(+) T lymphocytes.
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811894/the-conceptual-advances-of-carcinogenic-sequence-model-in-high-grade-serous-ovarian-cancer
#3
Hiroshi Kobayashi, Kana Iwai, Emiko Niiro, Sachiko Morioka, Yuki Yamada, Kenji Ogawa, Naoki Kawahara
The present review focuses on the current status of molecular pathology in high-grade serous cancer (HGSC) and preneoplastic conditions. This article reviews the English-language literature on HGSC, precursor, fallopian tubal epithelium, secretory cells, ciliated cells, secretory cell expansion, secretory cell outgrowth (SCOUT), p53 signature, serous tubal intraepithelial carcinoma (STIC), DNA damage and immunohistochemistry in an effort to identify the precursor-carcinoma sequence in HGSC. The majority of HGSC originates from the fimbriated end of the fallopian tube secretory epithelial cells, while the small part of this disease may develop from ovarian cortical inclusion cyst (CIC)...
September 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28811864/identification-of-four-oxidative-stress-responsive-micrornas-mir-34a-5p-mir-1915-3p-mir-638-and-mir-150-3p-in-hepatocellular-carcinoma
#4
Yong Wan, Ruixia Cui, Jingxian Gu, Xing Zhang, Xiaohong Xiang, Chang Liu, Kai Qu, Ting Lin
Increasing evidence suggests that oxidative stress plays an essential role during carcinogenesis. However, the underlying mechanism between oxidative stress and carcinogenesis remains unknown. Recently, microRNAs (miRNAs) are revealed to be involved in oxidative stress response and carcinogenesis. This study aims to identify miRNAs in hepatocellular carcinoma (HCC) cells which might involve in oxidative stress response. An integrated analysis of miRNA expression signature was performed by employing robust rank aggregation (RRA) method, and four miRNAs (miR-34a-5p, miR-1915-3p, miR-638, and miR-150-3p) were identified as the oxidative stress-responsive miRNAs...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28811661/myst2-kat7-histone-acetyltransferase-interaction-proteomics-reveals-tumour-suppressor-niam-as-a-novel-binding-partner-in-embryonic-stem-cells
#5
Mercedes Pardo, Lu Yu, Shihpei Shen, Peri Tate, Daniel Bode, Blake L Letney, Dawn E Quelle, William Skarnes, Jyoti S Choudhary
MYST histone acetyltransferases have crucial functions in transcription, replication and DNA repair and are hence implicated in development and cancer. Here we characterise Myst2/Kat7/Hbo1 protein interactions in mouse embryonic stem cells by affinity purification coupled to mass spectrometry. This study confirms that in embryonic stem cells Myst2 is part of H3 and H4 histone acetylation complexes similar to those described in somatic cells. We identify a novel Myst2-associated protein, the tumour suppressor protein Niam (Nuclear Interactor of ARF and Mdm2)...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811500/human-microcephaly-protein-rttn-interacts-with-stil-and-is-required-to-build-full-length-centrioles
#6
Hsin-Yi Chen, Chien-Ting Wu, Chieh-Ju C Tang, Yi-Nan Lin, Won-Jing Wang, Tang K Tang
Mutations in many centriolar protein-encoding genes cause primary microcephaly. Using super-resolution and electron microscopy, we find that the human microcephaly protein, RTTN, is recruited to the proximal end of the procentriole at early S phase, and is located at the inner luminal walls of centrioles. Further studies demonstrate that RTTN directly interacts with STIL and acts downstream of STIL-mediated centriole assembly. CRISPR/Cas9-mediated RTTN gene knockout in p53-deficient cells induce amplification of primitive procentriole bodies that lack the distal-half centriolar proteins, POC5 and POC1B...
August 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28811362/nuclear-envelope-rupture-is-enhanced-by-loss-of-p53-or-rb
#7
Zhe Yang, John Maciejowski, Titia de Lange
The mammalian nuclear envelope (NE) forms a stable physical barrier between the nucleus and the cytoplasm, normally breaking down only during the cell cycle phase of mitosis. However, spontaneous transient NE rupture in interphase can occur when NE integrity is compromised such as when the nucleus experiences mechanical stress. For instance, deficiencies in the nuclear lamins and their associated proteins can cause NE rupture that is promoted by forces exerted by actin filaments. NE rupture can allow cytoplasmic nucleases to access chromatin, potentially compromising genome integrity...
August 15, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28810294/-morphologic-features-of-fallopian-tubal-epithelium-in-pelvic-high-grade-serous-carcinoma
#8
R J Zhao, Y Y Wang, Z Li, K Y Wu, L F Kong, W X Zheng
Objective: To study the pathologic features of fallopian tubal epithelium in patients with pelvic high-grade serous carcinoma (HGSC), to investigate its role in pelvic serous carcinogenesis and to reclassify the primary site of HGSC based on recently proposed criteria. Methods: The fallopian tubes in 58 cases of pelvic HGSC (54 cases of ovarian primary, 3 cases of tubal primary, 1 case of peritoneum) and 25 cases of pelvic non-HGSC (5 cases of ovarian low-grade serous cancer, 9 cases of endometrioid cancer, and 11 cases of clear cell ovary carcinoma) were collected from June 2015 to December 2016, and serially examined under light microscope (SEE-FIM protocol)...
August 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/28809778/reprimo-a-potential-p53-dependent-tumor-suppressor-gene-is-frequently-hypermethylated-in-estrogen-receptor-%C3%AE-positive-breast-cancer
#9
Kurt Buchegger, Ismael Riquelme, Tamara Viscarra, Carmen Ili, Priscilla Brebi, Tim Hui-Ming Huang, Juan Carlos Roa
Aberrant DNA methylation is a hallmark of many cancers. Currently, there are four intrinsic molecular subtypes in breast cancer (BC): Luminal A, B, Her2-positive, and triple negative (TNBC). Recently, The Cancer Genome Atlas (TCGA) project has revealed that Luminal subtypes have higher levels of genome-wide methylation that may be a result of Estrogen/Estrogen receptor α (E2/ERα) signaling pathway activation. In this study, we analyze promoter CpG-island (CGIs) of the Reprimo (RPRM) gene in breast cancers (n = 77), cell lines (n = 38), and normal breast tissue (n = 10) using a MBDCap-seq database...
August 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28808383/chemopreventive-potential-of-major-flavonoid-compound-of-methanolic-bark-extract-of-saraca-asoca-roxb-in-benzene-induced-toxicity-of-acute-myeloid-leukemia-mice
#10
Manas Kumar Mukhopadhyay, Mithun Shaw, Debjani Nath
BACKGROUND: Saraca asoca (SA) (Roxb.) is one of the folk medicinal plants found in India, Bangladesh, and Sri Lanka. Its major biological activity appears due to the presence of flavonoid group of compounds in its bark extract. OBJECTIVE: In this study, our research aims to analyze the chemopreventive effect of flavonoids, especially a natural phenol catechin present in the bark methanolic extract of SA on acute myeloid leukemia (AML) mice. MATERIALS AND METHODS: The total bark extract was partitioned and analyzed on thin-layer chromatography (TLC) plate...
July 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28808340/kr%C3%A3-ppel-like-factor-6-is-a-transcriptional-activator-of-autophagy-in-acute-liver-injury
#11
Svenja Sydor, Paul Manka, Jan Best, Sami Jafoui, Jan-Peter Sowa, Miguel Eugenio Zoubek, Virginia Hernandez-Gea, Francisco Javier Cubero, Julia Kälsch, Diana Vetter, Maria Isabel Fiel, Yujin Hoshida, C Billie Bian, Leonard J Nelson, Han Moshage, Klaas Nico Faber, Andreas Paul, Hideo A Baba, Guido Gerken, Scott L Friedman, Ali Canbay, Lars P Bechmann
Krüppel-like factor 6 (KLF6) is a transcription factor and tumor suppressor. We previously identified KLF6 as mediator of hepatocyte glucose and lipid homeostasis. The loss or reduction of KLF6 is linked to the progression of hepatocellular carcinoma, but its contribution to liver regeneration and repair in acute liver injury are lacking so far. Here we explore the role of KLF6 in acute liver injury models in mice, and in patients with acute liver failure (ALF). KLF6 was induced in hepatocytes in ALF, and in both acetaminophen (APAP)- and carbon tetrachloride (CCl4)-treated mice...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808015/a-p53-dependent-response-limits-the-viability-of-mammalian-haploid-cells
#12
Teresa Olbrich, Cristina Mayor-Ruiz, Maria Vega-Sendino, Carmen Gomez, Sagrario Ortega, Sergio Ruiz, Oscar Fernandez-Capetillo
The recent development of haploid cell lines has facilitated forward genetic screenings in mammalian cells. These lines include near-haploid human cell lines isolated from a patient with chronic myelogenous leukemia (KBM7 and HAP1), as well as haploid embryonic stem cells derived from several organisms. In all cases, haploidy was shown to be an unstable state, so that cultures of mammalian haploid cells rapidly become enriched in diploids. Here we show that the observed diploidization is due to a proliferative disadvantage of haploid cells compared with diploid cells...
August 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28807825/usp3-stabilizes-p53-protein-through-its-deubiquitinase-activity
#13
Song Fu, Shize Shao, Longqiang Wang, Haijun Liu, Haitao Hou, Yanan Wang, Huan Wang, Xiangpeng Huang, Renhua Lv
p53 is the guardian of the genome integrity and the degradation of p53 protein is mediated by MDM2. Here we report that USP3 interacts with p53 and regulates p53 stability. Depletion of USP3 lead to accelerated degradation of p53 in normal cells thereby enhanced cell proliferation and transformation. Reconstitution of wildtype USP3, but not the USP3 C168S mutant, restored the stability of p53 protein and inhibited cell proliferation and transformation. These findings suggest that USP3 is an important regulator of p53 and regulates normal cell transformation...
August 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28807016/endogenous-controls-of-gene-expression-in-n-methyl-n-nitrosourea-induced-t-cell-lymphoma-in-p53-deficient-mice
#14
Xi Wu, Susu Liu, Jianjun Lyu, Shuya Zhou, Yanwei Yang, Chenfei Wang, Wenda Gu, Qin Zuo, Baowen Li, Changfa Fan
BACKGROUND: Real-time polymerase chain reaction (PCR) has become an increasingly important technique for gene expression profiling because it can provide insights into complex biological and pathological processes and be used to predict disease or treatment outcomes. Although normalized data are necessary for an accurate estimation of mRNA expression levels, several pieces of evidence suggest that the expression of so-called housekeeping genes is not stable. This study aimed to validate reference genes for the normalization of real-time PCR in an N-methyl-N-nitrosourea (MNU)-induced T-cell lymphoma mouse model...
August 14, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28806777/a-synthetic-sickness-screen-for-senescence-re-engagement-targets-in-mutant-cancer-backgrounds
#15
Claire J Cairney, Lauren S Godwin, Alan E Bilsland, Sharon Burns, Katrina H Stevenson, Lynn McGarry, John Revie, Jon D Moore, Ceri M Wiggins, Rebecca S Collinson, Clare Mudd, Elpida Tsonou, Mahito Sadaie, Dorothy C Bennett, Masashi Narita, Christopher J Torrance, W Nicol Keith
Senescence is a universal barrier to immortalisation and tumorigenesis. As such, interest in the use of senescence-induction in a therapeutic context has been gaining momentum in the past few years; however, senescence and immortalisation remain underserved areas for drug discovery owing to a lack of robust senescence inducing agents and an incomplete understanding of the signalling events underlying this complex process. In order to address this issue we undertook a large-scale morphological siRNA screen for inducers of senescence phenotypes in the human melanoma cell line A375P...
August 14, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28806397/mdm2-promotes-cdc25c-protein-degradation-and-delays-cell-cycle-progression-through-the-g2-m-phase
#16
L E Giono, L Resnick-Silverman, L A Carvajal, S St Clair, J J Manfredi
Upon different types of stress, the gene encoding the mitosis-promoting phosphatase Cdc25C is transcriptionally repressed by p53, contributing to p53's enforcement of a G2 cell cycle arrest. In addition, Cdc25C protein stability is also decreased following DNA damage. Mdm2, another p53 target gene, encodes a ubiquitin ligase that negatively regulates p53 levels by ubiquitination. Ablation of Mdm2 by siRNA led to an increase in p53 protein and repression of Cdc25C gene expression. However, Cdc25C protein levels were actually increased following Mdm2 depletion...
August 14, 2017: Oncogene
https://www.readbyqxmd.com/read/28805805/whole-tumor-section-quantitative-image-analysis-maximizes-between-pathologists-reproducibility-for-clinical-immunohistochemistry-based-biomarkers
#17
Michael Barnes, Chukka Srinivas, Isaac Bai, Judith Frederick, Wendy Liu, Anindya Sarkar, Xiuzhong Wang, Yao Nie, Bryce Portier, Monesh Kapadia, Olcay Sertel, Elizabeth Little, Bikash Sabata, Jim Ranger-Moore
Pathologists have had increasing responsibility for quantitating immunohistochemistry (IHC) biomarkers with the expectation of high between-reader reproducibility due to clinical decision-making especially for patient therapy. Digital imaging-based quantitation of IHC clinical slides offers a potential aid for improvement; however, its clinical adoption is limited potentially due to a conventional field-of-view annotation approach. In this study, we implemented a novel solely morphology-based whole tumor section annotation strategy to maximize image analysis quantitation results between readers...
August 14, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28805264/large-nested-variant-of-urothelial-carcinoma-a%C3%A2-clinicopathological-study-of-36-cases
#18
Eva Compérat, Jesse K McKenney, Arndt Hartmann, Ondrej Hes, Simone Bertz, Justine Varinot, Fadi Brimo
AIMS: The large nested variant of urothelial carcinoma (LNUC) has been added to the World Health Organization (WHO) 2016 classification. Scant data exist, and little is known about its clinical behaviour. MATERIAL AND RESULTS: Cases fulfilling the morphological criteria of LNUC were collected. Pure and mixed cases (i.e. with other patterns of invasive UC) were studied. Immunohistochemical staining with cytokeratin (CK)7, p63, GATA-3, CK20, p53 and Ki-67 was performed...
June 9, 2017: Histopathology
https://www.readbyqxmd.com/read/28805210/corrigendum-contribution-of-classical-end-joining-to-pten-inactivation-in-p53-mediated-glioblastoma-formation-and-drug-resistant-survival
#19
Youn-Jung Kang, Barbara Balter, Eva Csizmadia, Brian Haas, Himanshu Sharma, Roderick Bronson, Catherine T Yan
This corrects the article DOI: 10.1038/ncomms14013.
August 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28803777/paraoxonase-2-facilitates-pancreatic-cancer-growth-and-metastasis-by-stimulating-glut1-mediated-glucose-transport
#20
Arvindhan Nagarajan, Shaillay Kumar Dogra, Lisha Sun, Neeru Gandotra, Thuy Ho, Guoping Cai, Gary Cline, Priti Kumar, Robert A Cowles, Narendra Wajapeyee
Metabolic deregulation is a hallmark of human cancers, and the glycolytic and glutamine metabolism pathways were shown to be deregulated in pancreatic ductal adenocarcinoma (PDAC). To identify new metabolic regulators of PDAC tumor growth and metastasis, we systematically knocked down metabolic genes that were overexpressed in human PDAC tumor samples using short hairpin RNAs. We found that p53 transcriptionally represses paraoxonase 2 (PON2), which regulates GLUT1-mediated glucose transport via stomatin. The loss of PON2 initiates the cellular starvation response and activates AMP-activated protein kinase (AMPK)...
July 21, 2017: Molecular Cell
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