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https://www.readbyqxmd.com/read/28542143/dna-damage-and-s-phase-dependent-e2f1-stabilization-requires-the-ciap1-e3-ubiquitin-ligase-and-is-associated-with-k63-poly-ubiquitination-on-lysine-161-164-residues
#1
Valérie Glorian, Jennifer Allègre, Jean Berthelet, Baptiste Dumetier, Pierre-Marie Boutanquoi, Nathalie Droin, Cémile Kayaci, Jessy Cartier, Simon Gemble, Guillaume Marcion, Daniel Gonzalez, Romain Boidot, Carmen Garrido, Olivier Michaud, Eric Solary, Laurence Dubrez
The E2F transcription factor 1 is subtly regulated along the cell cycle progression and in response to DNA damage by post-translational modifications. Here, we demonstrated that the E3-ubiquitin ligase cellular inhibitor of apoptosis 1 (cIAP1) increases E2F1 K63-poly-ubiquitination on the lysine residue 161/164 cluster, which is associated with the transcriptional factor stability and activity. Mutation of these lysine residues completely abrogates the binding of E2F1 to CCNE, TP73 and APAF1 promoters, thus inhibiting transcriptional activation of these genes and E2F1-mediated cell proliferation control...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28480326/combining-oncolytic-virotherapy-with-p53-tumor-suppressor-gene-therapy
#2
REVIEW
Christian Bressy, Eric Hastie, Valery Z Grdzelishvili
Oncolytic virus (OV) therapy utilizes replication-competent viruses to kill cancer cells, leaving non-malignant cells unharmed. With the first U.S. Food and Drug Administration-approved OV, dozens of clinical trials ongoing, and an abundance of translational research in the field, OV therapy is poised to be one of the leading treatments for cancer. A number of recombinant OVs expressing a transgene for p53 (TP53) or another p53 family member (TP63 or TP73) were engineered with the goal of generating more potent OVs that function synergistically with host immunity and/or other therapies to reduce or eliminate tumor burden...
June 16, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28469092/transcriptional-dissection-of-melanoma-identifies-a-high-risk-subtype-underlying-tp53-family-genes-and-epigenome-deregulation
#3
Brateil Badal, Alexander Solovyov, Serena Di Cecilia, Joseph Minhow Chan, Li-Wei Chang, Ramiz Iqbal, Iraz T Aydin, Geena S Rajan, Chen Chen, Franco Abbate, Kshitij S Arora, Antoine Tanne, Stephen B Gruber, Timothy M Johnson, Douglas R Fullen, Leon Raskin, Robert Phelps, Nina Bhardwaj, Emily Bernstein, David T Ting, Georg Brunner, Eric E Schadt, Benjamin D Greenbaum, Julide Tok Celebi
BACKGROUND: Melanoma is a heterogeneous malignancy. We set out to identify the molecular underpinnings of high-risk melanomas, those that are likely to progress rapidly, metastasize, and result in poor outcomes. METHODS: We examined transcriptome changes from benign states to early-, intermediate-, and late-stage tumors using a set of 78 treatment-naive melanocytic tumors consisting of primary melanomas of the skin and benign melanocytic lesions. We utilized a next-generation sequencing platform that enabled a comprehensive analysis of protein-coding and -noncoding RNA transcripts...
May 4, 2017: JCI Insight
https://www.readbyqxmd.com/read/28403886/the-long-non-coding-rna-tp73-as1-modulates-hcc-cell-proliferation-through-mir-200a-dependent-hmgb1-rage-regulation
#4
Shaling Li, Yan Huang, Yun Huang, Yongming Fu, Daolin Tang, Rui Kang, Rongrong Zhou, Xue-Gong Fan
BACKGROUND: P73 antisense RNA 1 T (non-protein coding), also known as TP73-AS1, is a long non-coding RNA (lncRNA) which is involved in cell proliferation and the development of tumors. However, the exact effects and molecular mechanisms of TP73-AS1 in hepatocellular carcinoma (HCC) progression are still unknown. The present study is aimed to investigate the detailed functions and the mechanism of TP73-AS1 in regulation of HCC cell proliferation. METHODS: TP73-AS1 expression in HCC tissues and cell lines was determined using real-time PCR assays; the correlation of TP73-AS1 expression with clinicopathological features of HCC was analyzed...
April 12, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28379612/the-long-non-coding-rna-tp73-as1-interacted-with-mir-142-to-modulate-brain-glioma-growth-through-hmgb1-rage-pathway
#5
Rong Zhang, Hekun Jin, Fan Lou
P73 antisense RNA 1T (non-protein coding), also known as TP73-AS1 or PDAM, is a long non-coding RNA which may regulate apoptosis via regulation of p53-dependent anti-apoptotic genes. An abnormal change of TP73-AS1 expression was noticed in cancers. The effects of TP73-AS1 in brain glioma growth and the underlying mechanism remain unclear so far. In the present study, TP73-AS1 was specifically upregulated in brain glioma tissues and cell lines and was associated with poorer prognosis in patients with glioma...
April 5, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28303856/effect-of-matrix-metallopeptidase-13-on-the-function-of-mouse-bone-marrow-derived-dendritic-cells
#6
Xiao-Dong Li, Xin-Rui Zhang, Zhi-Hao Li, Yang Yang, Duo Zhang, Heng Zheng, Shu-Ying Dong, Juan Chen, Xian-Dong Zeng
BACKGROUND: Dendritic cells are professional antigen-presenting cells found in an immature state in epithelia and interstitial space, where they capture antigens such as pathogens or damaged tissue. Matrix metallopeptidase 13 (MMP-13), a member of the collagenase subfamily, is involved in many different cellular processes and is expressed in murine bone marrow-derived dendritic cells (DCs). The function of MMP-13 in DCs is not well understood. Here, we investigated the effect of MMP-13 on DC maturation, apoptosis, and phagocytosis...
March 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28258440/comprehensive-characterization-of-genes-associated-with-the-tp53-signal-transduction-pathway-in-various-tumors
#7
Shumpei Ohnami, Keiichi Ohshima, Takeshi Nagashima, Kenichi Urakami, Yuji Shimoda, Junko Saito, Akane Naruoka, Keiichi Hatakeyama, Tohru Mochizuki, Masakuni Serizawa, Sumiko Ohnami, Masatoshi Kusuhara, Ken Yamaguchi
The TP53 signal transduction pathway is an attractive target for cancer treatments. In this study, we conducted a comprehensive molecular evaluation of 907 patients with cancer in Japan to identify genomic alterations in the TP53 pathway. TP53 mutations were frequently detected in many cancers, except melanoma, thymic tumors, gastrointestinal stromal tumors, and renal cancers. The frequencies of non-synonymous single nucleotide variants (SNVs) in the TP53 family members TP63 and TP73 were relatively low, although genes with increased frequencies of SNVs were as follows: PTEN (11...
March 3, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28168356/identifying-survival-associated-modules-from-the-dysregulated-triplet-network-in-glioblastoma-multiforme
#8
Jia-Bin Wang, Feng-Hua Liu, Jian-Hang Chen, Hai-Tao Ge, Lu-Yan Mu, Hong-Bo Bao, Zhi-Guo Lin
BACKGROUND: Long noncoding RNAs (lncRNAs) can act as competitive endogenous RNAs (ceRNAs) to compete with mRNAs for binding miroRNAs (miRNAs). The dysregulated triplets, composed by mRNAs, lncRNAs, and miRNAs, contributed to the development and progression of diseases, such as cancer. However, the roles played by triplet biomarkers are not fully understand in glioblastoma multiforme (GBM) patient survival. OBJECTIVES: Here, we constructed a differential triplet interaction network (TriNet) between GBM and normal tissues and identified GBM survival related triplets...
April 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28129457/tumor-suppressor-gene-methylation-on-the-short-arm-of-chromosome-1-in-chronic-myelogenous-leukemia
#9
Naoki Mori, Mari Ohwashi-Miyazaki, Kentaro Yoshinaga, Michiko Okada, Masayuki Shiseki, Toshiko Motoji, Junji Tanaka
OBJECTIVES: We previously reported loss of heterozygosity on 1p in chronic myelogenous leukemia (CML). We analyzed promoter methylation and mutation of tumor suppressor genes on 1p36 in CML. METHODS: We performed methylation-specific PCR (MS-PCR) analysis of the PRDM2, RUNX3, and TP73 genes in 61 patients with CML (43 chronic phase, CP; two accelerated phase; and 16 blast crisis, BC). Oxidative MS-PCR, PCR-single-strand conformation polymorphism, and real-time reverse transcriptase PCR were also analyzed...
January 27, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28128397/meta-analysis-of-tp73-polymorphism-and-cervical-cancer
#10
H Feng, L Sui, M Du, Q Wang
The aim of this study was to investigate the tumor protein p73 (TP73) G4C14-A4T14 polymorphism and to perform a meta-analysis to assess TP73 expression in cervical cancer and precancerous tissue. Articles containing data regarding TP73 status in cervical cancer patients and healthy controls were retrieved from PubMed, EMBASE, Cochrane, Chinese Biomedical Literature, and China National Knowledge Infrastructure databases. Then, the quality of the studies was evaluated according to inclusion and exclusion criteria...
January 23, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27698933/screening-of-pleural-mesotheliomas-for-dna-damage-repair-players-by-digital-gene-expression-analysis-can-enhance-clinical-management-of-patients-receiving-platin-based-chemotherapy
#11
Robert Fred Henry Walter, Claudia Vollbrecht, Robert Werner, Thomas Mairinger, Jan Schmeller, Elena Flom, Jeremias Wohlschlaeger, Nikolaos Barbetakis, Dimitrios Paliouras, Fotios Chatzinikolaou, Vasilis Adamidis, Kosmas Tsakiridis, Paul Zarogoulidis, Georgia Trakada, Daniel Christian Christoph, Kurt Werner Schmid, Fabian Dominik Mairinger
BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare, predominantly asbestos-related and biologically highly aggressive tumour leading to a dismal prognosis. Multimodality therapy consisting of platinum-based chemotherapy is the treatment of choice. The reasons for the rather poor efficacy of platinum compounds remain largely unknown. MATERIAL AND METHODS: For this exploratory mRNA study, 24 FFPE tumour specimens were screened by digital gene expression analysis...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27671304/dehydroleucodine-induces-a-tp73-dependent-transcriptional-regulation-of-multiple-cell-death-target-genes-in-human-glioblastoma-cells
#12
Edward A Ratovitski
BACKGROUND: Dehydroleucodine, a natural sesquiterpene lactone from Artemisia douglassiana Besser (Argentine) and Gynoxys verrucosa (Ecuador). OBJECTIVE: To define the molecular mechanisms underlying the effect of dehydroleucodine on the human glioblastoma cells. METHOD: Various techniques (cDNA expression array, real-time quantitative PCR, chromatin immunprecipitation, luciferase reporter assay, use of phosphospecific antibodies, immunoprecipitation, immunoblotting, apoptosis and autophagy assays) were employed to define and validate multiple molecular gene targets affected in human glioblastoma cells upon dehydroleucodine exposure...
2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/27533450/prima-1-targets-the-vulnerability-of-multiple-myeloma-of-deregulated-protein-homeostasis-through-the-perturbation-of-er-stress-via-p73-demethylation
#13
Phaik Ju Teoh, Chonglei Bi, Chirackal Sintosebastian, Liang Seah Tay, Rafael Fonseca, Wee Joo Chng
Despite therapeutic advancement, multiple myeloma (MM) remains incurable with drug resistance being one of the main challenges in the clinic. Myeloma cells possess high protein secretory load, leading to increased intracellular endoplasmic reticulum (ER) stress. Hence, they are vulnerable to further perturbation to its protein homeostasis. In studying the therapeutic mechanism of PRIMA-1 (mutant-p53-reactivating-agent), we uncovered its novel p53-independent-mechanism that can be exploited for myeloma. Despite its inability in restoring the wild type-p53 protein conformation and transcriptional function in the mutant-p53-human-myeloma-cells, PRIMA-1 was efficacious against myeloma cells with differential p53 genotypes...
September 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27516190/importance-of-tumour-suppressor-gene-methylation-in-sinonasal-carcinomas
#14
M Chmelařová, I Sirák, M Mžik, K Sieglová, H Vošmiková, P Dundr, K Němejcová, J Michálek, M Vošmik, V Palička, J Laco
Epigenetic changes are considered to be a frequent event during tumour development. Hypermethylation of promoter CpG islands represents an alternative mechanism for inactivation of tumour suppressor genes, DNA repair genes, cell cycle regulators and transcription factors. The aim of this study was to investigate promoter methylation of specific genes in samples of sinonasal carcinoma by comparison with normal sinonasal tissue. To search for epigenetic events we used methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) to compare the methylation status of 64 tissue samples of sinonasal carcinomas with 19 control samples...
2016: Folia Biologica (Praha)
https://www.readbyqxmd.com/read/27308533/novel-role-of-p73-as-a-regulator-of-developmental-angiogenesis-implication-for-cancer-therapy
#15
Maria C Marin, Margarita M Marques
Information regarding the role of p73 in the regulation of angiogenesis has been incomplete and quite controversial. Remarkably, several groups, including ours, have recently demonstrated that TP73 plays a fundamental role in angiogenesis regulation and that differential expression of TP73 could have important consequences in tumor angiogenesis. Here, we discuss a possible model for p73 function in the regulation of developmental angiogenesis and tumor angiogenesis.
January 2016: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/27257214/tap73-is-a-central-transcriptional-regulator-of-airway-multiciliogenesis
#16
Alice Nemajerova, Daniela Kramer, Saul S Siller, Christian Herr, Orr Shomroni, Tonatiuh Pena, Cristina Gallinas Suazo, Katharina Glaser, Merit Wildung, Henrik Steffen, Anusha Sriraman, Fabian Oberle, Magdalena Wienken, Magali Hennion, Ramon Vidal, Bettina Royen, Mihai Alevra, Detlev Schild, Robert Bals, Jürgen Dönitz, Dietmar Riedel, Stefan Bonn, Ken-Ichi Takemaru, Ute M Moll, Muriel Lizé
Motile multiciliated cells (MCCs) have critical roles in respiratory health and disease and are essential for cleaning inhaled pollutants and pathogens from airways. Despite their significance for human disease, the transcriptional control that governs multiciliogenesis remains poorly understood. Here we identify TP73, a p53 homolog, as governing the program for airway multiciliogenesis. Mice with TP73 deficiency suffer from chronic respiratory tract infections due to profound defects in ciliogenesis and complete loss of mucociliary clearance...
June 1, 2016: Genes & Development
https://www.readbyqxmd.com/read/27246533/the-study-of-the-relation-of-dna-repair-pathway-genes-snps-and-the-sensitivity-to-radiotherapy-and-chemotherapy-of-nsclc
#17
Chunbo Wang, Huan Nie, Yiqun Li, Guiyou Liu, Xu Wang, Shijie Xing, Liping Zhang, Xin Chen, Yue Chen, Yu Li
To analyze the relation between SNPs in DNA repair pathway-related genes and sensitivity of tumor radio-chemotherapy, 26 SNPs in 20 DNA repair genes were genotyped on 176 patients of NSCLC undertaking radio-chemotherapy treatment. In squamous cell carcinoma (SCC), as the rs2228000, rs2228001 (XPC), rs2273953 (TP73), rs2279744 (MDM2), rs2299939 (PTEN) and rs8178085, rs12334811 (DNA-PKcs) affected the sensitivity to chemotherapy, so did the rs8178085, rs12334811 to radiotherapy. Moreover rs344781, rs2273953 and rs12334811 were related with the survival time of SCC...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27132513/tnf-%C3%AE-modulates-genome-wide-redistribution-of-%C3%AE-np63%C3%AE-tap73-and-nf-%C3%AE%C2%BAb-crel-interactive-binding-on-tp53-and-ap-1-motifs-to-promote-an-oncogenic-gene-program-in-squamous-cancer
#18
H Si, H Lu, X Yang, A Mattox, M Jang, Y Bian, E Sano, H Viadiu, B Yan, C Yau, S Ng, S K Lee, R-A Romano, S Davis, R L Walker, W Xiao, H Sun, L Wei, S Sinha, C C Benz, J M Stuart, P S Meltzer, C Van Waes, Z Chen
The Cancer Genome Atlas (TCGA) network study of 12 cancer types (PanCancer 12) revealed frequent mutation of TP53, and amplification and expression of related TP63 isoform ΔNp63 in squamous cancers. Further, aberrant expression of inflammatory genes and TP53/p63/p73 targets were detected in the PanCancer 12 project, reminiscent of gene programs comodulated by cREL/ΔNp63/TAp73 transcription factors we uncovered in head and neck squamous cell carcinomas (HNSCCs). However, how inflammatory gene signatures and cREL/p63/p73 targets are comodulated genome wide is unclear...
November 3, 2016: Oncogene
https://www.readbyqxmd.com/read/27105536/growth-suppression-by-myc-inhibition-in-small-cell-lung-cancer-cells-with-tp53-and-rb1-inactivation
#19
Francesco Paolo Fiorentino, Elvan Tokgün, Sònia Solé-Sánchez, Sabrina Giampaolo, Onur Tokgün, Toni Jauset, Takashi Kohno, Manuel Perucho, Laura Soucek, Jun Yokota
Small cell lung cancer (SCLC) is the most aggressive type of lung cancer with high mortality. One of the MYC family genes, MYC, MYCL or MYCN, is amplified in ~20% of the SCLCs; therefore, MYC proteins are potential therapeutic targets in SCLC patients. We investigated the therapeutic impact of Omomyc, a MYC dominant negative, in a panel of SCLC cell lines. Strikingly, Omomyc suppressed the growth of all tested cell lines by inducing cell cycle arrest and/or apoptosis. Induction of G1 arrest by Omomyc was found to be dependent on the activation of CDKN1A, in part, through the TP73 pathway...
May 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27018246/molecular-analysis-of-apoptosis-pathway-after-photodynamic-therapy-in-breast-cancer-animal-model-study
#20
Luciana C Silva, Juliana Ferreira-Strixino, Letícia C Fontana, António M d'A Rocha Gonsalves, Arménio C Serra, Marta Pineiro, Renata A Canevari
BACKGROUND: Molecular investigation of breast tumors has permitted better understanding about interaction of genes and pathways involved in tumor progression. OBJECTIVE: The aim of this study was to evaluate the association between genes belonging to the pathway of apoptosis with tumor response to photodynamic therapy. STUDY DESIGN/MATERIALS AND METHODS: The mammary tumors were induced in twenty-four Spraguey-Dawley female rats by oral gavage of 7,12-dimethylbenz(a)anthracene (8mg/Kg body weight)...
June 2016: Photodiagnosis and Photodynamic Therapy
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