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https://www.readbyqxmd.com/read/27892792/e2fl1-is-a-meiosis-specific-transcription-factor-in-the-protist-tetrahymena-thermophila
#1
Jing Zhang, Miao Tian, Guan-Xiong Yan, Anura Shodhan, Wei Miao
Members of the E2F family of transcription factors have been reported to regulate the expression of genes involved in cell cycle control, DNA replication, and DNA repair in multicellular eukaryotes. Here, E2FL1, a meiosis-specific E2F transcription factor gene, was identified in the model ciliate Tetrahymena thermophila. Loss of this gene resulted in meiotic arrest prior to anaphase I. The cytological experiments revealed that the meiotic homologous pairing was not affected in the absence of E2FL1, but the paired homologous chromosomes did not separate and assumed a peculiar tandem arrangement...
November 28, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27888801/common-profiles-of-notch-signaling-differentiate-disease-free-survival-in-luminal-type-a-and-triple-negative-breast-cancer
#2
Magdalena Orzechowska, Dorota Jędroszka, Andrzej K Bednarek
Breast cancer (BC) is characterized by high heterogeneity regarding its biology and clinical characteristics. The Notch pathway regulates such processes as organ modeling and epithelial-to-mesenchymal transition (EMT).The aim of the study was to determine the effect of differential expression of Notch members on disease-free survival (DFS) in luminal type A (lumA) and triple negative (TN) BC.The differential expression of 19 Notch members was examined in a TCGA BC cohort. DFS analysis was performed using the log-rank test (p<0...
November 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27888102/the-phosphatidyl-inositol-3-kinase-pathway-does-not-suppress-activation-of-the-arf-and-bim-genes-by-deregulated-e2f1-activity
#3
Kenta Kurayoshi, Junko Okuno, Eiko Ozono, Ritsuko Iwanaga, Andrew P Bradford, Kazuyuki Kugawa, Keigo Araki, Kiyoshi Ohtani
The transcription factor E2F plays crucial roles in tumor suppression by activating pro-apoptotic genes such as the tumor suppressor ARF. The regulation of the ARF gene is distinct from that of growth-related E2F targets, in that it is specifically activated by deregulated E2F activity, induced by over-expression of E2F or forced inactivation of pRB, but not by physiological E2F activity induced by growth stimulation. The phosphatidyl inositol 3 kinase (PI3K) pathway was reported to suppress expression of some atypical pro-apoptotic genes by over-expressed E2F1...
November 22, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27864908/e2f-transcription-factor-2-variants-as-predictive-biomarkers-for-recurrence-risk-in-patients-with-squamous-cell-carcinoma-of-the-oropharynx
#4
Yuncheng Li, Erich M Sturgis, Lijun Zhu, Xiaoli Cao, Qingyi Wei, Hua Zhang, Guojun Li
Because E2F transcription factor 2 (E2F2) promoter polymorphisms have been implicated in carcinogenesis and prognosis, we investigated associations between genetic variants in five E2F2 promoter polymorphisms and recurrence risk of squamous cell carcinoma of the oropharynx (SCCOP) in 1,008 patients. A log-rank test and multivariable Cox models were used to assess the associations. Compared with patients with variant genotypes of E2F2-rs2742976 and E2F2-rs3218123, patients with common homozygous genotypes had better disease-free survival (both log-rank, p < 0...
November 19, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27858503/high-throughput-sequencing-of-two-populations-of-extracellular-vesicles-provides-an-mrna-signature-that-can-be-detected-in-the-circulation-of-breast-cancer-patients
#5
Andrew Conley, Valentina R Minciacchi, Dhong Hyun Lee, Beatrice S Knudsen, Beth Y Karlan, Luigi Citrigno, Giuseppe Viglietto, Muneesh Tewari, Michael R Freeman, Francesca Demichelis, Dolores Di Vizio
Extracellular vesicles (EVs) contain a wide range of RNA types with a reported prevalence of non-coding RNA. To date a comprehensive characterization of the protein coding transcripts in EVs is still lacking. We performed RNA-Sequencing (RNA-Seq) of two EV populations and identified a small fraction of transcripts that were expressed at significantly different levels in large oncosomes and exosomes, suggesting they may mediate specialized functions. However, these two EV populations exhibited a common mRNA signature that, in comparison to their donor cells, was significantly enriched in mRNAs encoding E2F transcriptional targets and histone proteins...
November 18, 2016: RNA Biology
https://www.readbyqxmd.com/read/27821477/interchangeable-roles-for-e2f-transcriptional-repression-by-the-retinoblastoma-protein-and-p27kip1-cdk-regulation-in-cell-cycle-control-and-tumor-suppression
#6
Michael J Thwaites, Matthew J Cecchini, Daniel T Passos, Ian Welch, Frederick A Dick
The mammalian G1-S phase transition is controlled by the opposing forces of cyclin dependent kinases (CDK) and the retinoblastoma protein (pRB). Here we present evidence for systems level control of cell cycle arrest by pRB-E2F and p27-CDK regulation. By introducing a point mutant allele of pRB that is defective for E2F repression (Rb1(G)) into a p27(KIP1) null background (Cdkn1b(-/-)), both E2F transcriptional repression and CDK regulation are compromised. These double mutant Rb1(G/G); Cdkn1b(-/-) mice are viable and phenocopy Rb1(+/-) mice in developing pituitary adenocarcinomas, even though neither single mutant strain is cancer prone...
November 7, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27819669/a-cdk2-activity-signature-predicts-outcome-in-cdk2-low-cancers
#7
S R McCurdy, M Pacal, M Ahmad, R Bremner
The role of cyclin-dependent kinase 2 (CDK2) in cancer is controversial. A major hurdle is the availability of tools to easily assess its activity across many samples. Here, we introduce a transcriptional signature to specifically track CDK2 activity. It responds to genetic and chemical perturbations in the CDK-RB-E2F axis, correlates with mitotic rate in vitro and in vivo and reacts rapidly to changes in CDK2 activity during cell cycle progression. We find that CDK2 activity is specifically elevated in human testes, mirroring its critical function in mice, and report very distinct profiles across human cancers...
November 7, 2016: Oncogene
https://www.readbyqxmd.com/read/27816815/dreams-make-plant-cells-to-cycle-or-to-become-quiescent
#8
REVIEW
Zoltán Magyar, László Bögre, Masaki Ito
Cell cycle phase specific oscillation of gene transcription has long been recognized as an underlying principle for ordered processes during cell proliferation. The G1/S-specific and G2/M-specific cohorts of genes in plants are regulated by the E2F and the MYB3R transcription factors. Mutant analysis suggests that activator E2F functions might not be fully required for cell cycle entry. In contrast, the two activator-type MYB3Rs are part of positive feedback loops to drive the burst of mitotic gene expression, which is necessary at least to accomplish cytokinesis...
November 3, 2016: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/27802335/e2f1-and-tfdp1-regulate-pitx1-expression-in-normal-and-osteoarthritic-articular-chondrocytes
#9
Martin Pellicelli, Cynthia Picard, DaShen Wang, Patrick Lavigne, Alain Moreau
We previously reported a loss-of-PITX1 expression in patients suffering of knee/hip osteoarthritis (OA). Search for the mechanism underlying this event led us to discover that PITX1 repression was triggered by the aberrant nuclear accumulation of Prohibitin (PHB1), an E2F1 co-repressor, in OA articular chondrocytes. In the current study, we assessed in details the involvement of E2F transcription factors in regulating PITX1 expression. We also analyzed other genes that are similarly regulated by E2F in regard to osteoarthritis...
2016: PloS One
https://www.readbyqxmd.com/read/27801668/upregulation-of-mir-99a-is-associated-with-poor-prognosis-of-acute-myeloid-leukemia-and-promotes-myeloid-leukemia-cell-expansion
#10
Xiaohui Si, Xiaoyun Zhang, Xing Hao, Yunan Li, Zizhen Chen, Yahui Ding, Hui Shi, Jie Bai, Yingdai Gao, Tao Cheng, Feng-Chun Yang, Yuan Zhou
Leukemia stem cells (LSCs) can resist available treatments that results in disease progression and/or relapse. To dissect the microRNA (miRNA) expression signature of relapse in acute myeloid leukemia (AML), miRNA array analysis was performed using enriched LSCs from paired bone marrow samples of an AML patient at different disease stages. We identified that miR-99a was significantly upregulated in the LSCs obtained at relapse compared to the LSCs collected at the time of initial diagnosis. We also found that miR-99a was upregulated in LSCs compared to non-LSCs in a larger cohort of AML patients, and higher expression levels of miR-99a were significantly correlated with worse overall survival and event-free survival in these AML patients...
October 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27795708/broad-spectrum-anticancer-activity-of-myo-inositol-and-inositol-hexakisphosphate
#11
REVIEW
Mariano Bizzarri, Simona Dinicola, Arturo Bevilacqua, Alessandra Cucina
Inositols (myo-inositol and inositol hexakisphosphate) exert a wide range of critical activities in both physiological and pathological settings. Deregulated inositol metabolism has been recorded in a number of diseases, including cancer, where inositol modulates different critical pathways. Inositols inhibit pRB phosphorylation, fostering the pRB/E2F complexes formation and blocking progression along the cell cycle. Inositols reduce PI3K levels, thus counteracting the activation of the PKC/RAS/ERK pathway downstream of PI3K activation...
2016: International Journal of Endocrinology
https://www.readbyqxmd.com/read/27795297/e2f-2-promotes-nuclear-condensation-and-enucleation-of-terminally-differentiated-erythroblasts
#12
Kelsey L Swartz, Scott N Wood, Tushar Murthy, Oscar Ramirez, Gangjian Qin, Manoj M Pillai, Sridhar Rao, Alex C Minella
E2F-2 is a Retinoblastoma (Rb)-regulated transcription factor induced during terminal erythroid maturation. Cyclin E-mediated Rb hyper-phosphorylation induces E2F transcriptional activator functions. We previously reported that deregulated cyclin E activity causes defective terminal maturation of nucleated erythroblasts in vivo. Here, we find these defects are normalized by E2F-2 deletion; however, anemia in mice with deregulated cyclin E is not improved by E2F-2-loss, which itself causes reduced peripheral red blood cell (RBC) counts, without altering relative abundances of erythroblast subpopulations...
October 17, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27789274/h19-noncoding-rna-an-independent-prognostic-factor-regulates-essential-rb-e2f-and-cdk8-%C3%AE-catenin-signaling-in-colorectal-cancer
#13
Masahisa Ohtsuka, Hui Ling, Cristina Ivan, Martin Pichler, Daisuke Matsushita, Matthew Goblirsch, Verena Stiegelbauer, Kunitoshi Shigeyasu, Xinna Zhang, Meng Chen, Fnu Vidhu, Geoffrey A Bartholomeusz, Yuji Toiyama, Masato Kusunoki, Yuichiro Doki, Masaki Mori, Shumei Song, Jillian R Gunther, Sunil Krishnan, Ondrej Slaby, Ajay Goel, Jaffer A Ajani, Milan Radovich, George A Calin
The clinical significance of long noncoding RNAs (lncRNAs) in colorectal cancer (CRC) remains largely unexplored. Here, we analyzed a large panel of lncRNA candidates with The Cancer Genome Atlas (TCGA) CRC dataset, and identified H19 as the most significant lncRNA associated with CRC patient survival. We further validated such association in two independent CRC cohorts. H19 silencing blocked G1-S transition, reduced cell proliferation, and inhibited cell migration. We profiled gene expression changes to gain mechanism insight of H19 function...
October 19, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27771561/proteomic-analysis-of-the-gamma-human-papillomavirus-type-197-e6-and-e7-associated-cellular-proteins
#14
Miranda Grace, Karl Munger
Gamma HPV197 was the most frequently identified HPV when human skin cancer specimens were analyzed by deep sequencing (Arroyo Muhr et al., Int. J. Cancer 136: 2546-55, 2015). To gain insight into the biological activities of HPV197, we investigated the cellular interactomes of HPV197 E6 and E7. HPV197 E6 protein interacts with a broad spectrum of cellular LXXLL domain proteins, including UBE3A and MAML1. HPV197 E6 also binds and inhibits the TP53 tumor suppressor and interacts with the CCR4-NOT ubiquitin ligase and deadenylation complex...
January 2017: Virology
https://www.readbyqxmd.com/read/27756884/early2-factor-e2f-deregulation-is-a-prognostic-and-predictive-biomarker-in-lung-adenocarcinoma
#15
Lu Chen, Courtney A Kurtyka, Eric A Welsh, Jason I Rivera, Brienne E Engel, Teresita Muñoz-Antonia, Sean J Yoder, Steven A Eschrich, Ben C Creelan, Alberto A Chiappori, Jhanelle E Gray, Jose Luis Ramirez, Rafael Rosell, Matthew B Schabath, Eric B Haura, Dung-Tsa Chen, W Douglas Cress
Clinicians routinely prescribe adjuvant chemotherapy (ACT) for resected non-small cell lung cancer patients. However, ACT only improves five-year disease-free survival in stage I-III non-small cell lung cancer by 5-15%, with most patients deriving no benefit. Herein, deregulation of the E2F pathway was explored as a biomarker in lung adenocarcinoma patients. An E2F pathway scoring system, based on 74 E2F-regulated genes, was trained for RNA from two platforms: fresh-frozen (FF) or formalin-fixed paraffin-embedded (FFPE) tissues...
October 14, 2016: Oncotarget
https://www.readbyqxmd.com/read/27753528/novel-functions-for-the-transcription-factor-e2f4-in-development-and-disease
#16
Jenny Hsu, Julien Sage
The E2F family of transcription factors is a key determinant of cell proliferation in response to extra- and intra-cellular signals. Within this family, E2F4 is a transcriptional repressor whose activity is critical to engage and maintain cell cycle arrest in G0/G1 in conjunction with members of the retinoblastoma (RB) family. However, recent observations challenge this paradigm and indicate that E2F4 has a multitude of functions in cells besides this cell cycle regulatory role, including in embryonic and adult stem cells, during regenerative processes, and in cancer...
October 18, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27741518/acrolein-preferentially-damages-nucleolus-eliciting-ribosomal-stress-and-apoptosis-in-human-cancer-cells
#17
Hsiang-Tsui Wang, Tzu-Ying Chen, Ching-Wen Weng, Chun-Hsiang Yang, Moon-Shong Tang
Acrolein (Acr) is a potent cytotoxic and DNA damaging agent which is ubiquitous in the environment and abundant in tobacco smoke. Acr is also an active cytotoxic metabolite of the anti-cancer drugs cyclophosphamide and ifosfamide. The mechanisms via which Acr exerts its anti-cancer activity and cytotoxicity are not clear. In this study, we found that Acr induces cytotoxicity and cell death in human cancer cells with different activities of p53. Acr preferentially binds nucleolar ribosomal DNA (rDNA) to form Acr-deoxyguanosine adducts, and induces oxidative damage to both rDNA and ribosomal RNA (rRNA)...
October 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27708231/deregulation-of-the-prb-e2f4-axis-alters-epidermal-homeostasis-and-favors-tumor-development
#18
Clotilde Costa, Mirentxu Santos, Mónica Martínez-Fernández, Corina Lorz, Sara Lázaro, Jesús M Paramio
E2F/RB activity is altered in most human tumors. The retinoblastoma family of proteins plays a key role in regulating the progression of the cell cycle from the G1 to S phases. This is achieved through negative regulation of E2F transcription factors, important positive regulators of cell cycle entry. E2F family members are divided into two groups: activators (E2F1-E2F3a) and repressors (E2F3b-E2F8). E2F4 accounts for a large part of the E2F activity and is a main E2F repressor member in vivo. Perturbations in the balance from quiescence towards proliferation contribute to increased mitotic gene expression levels frequently observed in cancer...
September 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27708221/prmt5-competitively-binds-to-cdk4-to-promote-g1-s-transition-upon-glucose-induction-in-hepatocellular-carcinoma
#19
Hao Yang, Xiaoping Zhao, Li Zhao, Liu Liu, Jiajin Li, Wenzhi Jia, Jianjun Liu, Gang Huang
Although cancer cells are known to be "addicted" to glucose, the effect of glucose in proliferation of these cells remains elusive. Here, we report that upon glucose induction, protein arginine methyltransferase 5 (PRMT5) exerts a profound effect on the G1-S cell cycle progression via directly interacting with cyclin dependent kinase 4 (CDK4) in hepatocellular carcinoma (HCC). Upregulation of both PRMT5 and CDK4 predicts more malignant characteristics in human HCC tissues. Mechanistically, glucose promotes the interaction between PRMT5 and CDK4, which leads to activation of CDK4-RB-E2F-mediated transcription via releasing CDKN2A from CDK4...
September 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27704360/e2f-1-promotes-dapk2-induced-anti-tumor-immunity-of-gastric-cancer-cells-by-targeting-mir-34a
#20
Lin-Hai Yan, Zhi-Ning Chen, Li Li, Jia Chen, Xian-Wei Mo, Yu-Zhou Qin, Wen-E Wei, Hai-Quan Qin, Yuan Lin, Jian-Si Chen
Activation of the transcription factor E2F-1 gene is a negative event in dendritic cell (DC) maturation process. Down-regulation of E2F1 causes immaturity of DC thereby stopping antigen production which in turn leads to inhibition of immune responses. E2F-1-free stimulates the NF-kB signaling pathway, leading to activation of monocytes and several other transcription factor genes. In the study, we report that down-regulation of E2F-1 in DCs promote anti-tumor immune response in gastric cancer (GC) cells through a novel mechanism...
October 4, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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