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https://www.readbyqxmd.com/read/28723554/hypoxia-sensitive-commd1-integrates-signaling-and-cellular-metabolism-in-human-macrophages-and-suppresses-osteoclastogenesis
#1
Koichi Murata, Celestia Fang, Chikashi Terao, Eugenia G Giannopoulou, Ye Ji Lee, Min Joon Lee, Se-Hwan Mun, Seyeon Bae, Yu Qiao, Ruoxi Yuan, Moritoshi Furu, Hiromu Ito, Koichiro Ohmura, Shuichi Matsuda, Tsuneyo Mimori, Fumihiko Matsuda, Kyung-Hyun Park-Min, Lionel B Ivashkiv
Hypoxia augments inflammatory responses and osteoclastogenesis by incompletely understood mechanisms. We identified COMMD1 as a cell-intrinsic negative regulator of osteoclastogenesis that is suppressed by hypoxia. In human macrophages, COMMD1 restrained induction of NF-κB signaling and a transcription factor E2F1-dependent metabolic pathway by the cytokine RANKL. Downregulation of COMMD1 protein expression by hypoxia augmented RANKL-induced expression of inflammatory and E2F1 target genes and downstream osteoclastogenesis...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28701722/asxl1-deficiency-in-embryonic-fibroblasts-leads-to-cellular-senescence-via-impairment-of-the-akt-e2f-pathway-and-ezh2-inactivation
#2
Hye Sook Youn, Tae-Yoon Kim, Ui-Hyun Park, Seung-Tae Moon, So-Jung An, Yong-Kyu Lee, Jin-Taek Hwang, Eun-Joo Kim, Soo-Jong Um
Although ASXL1 mutations are frequently found in human diseases, including myeloid leukemia, the cell proliferation-associated function of ASXL1 is largely unknown. Here, we explored the molecular mechanism underlying the growth defect found in Asxl1-deficient mouse embryonic fibroblasts (MEFs). We found that Asxl1, through amino acids 371 to 655, interacts with the kinase domain of AKT1. In Asxl1-null MEFs, IGF-1 was unable to induce AKT1 phosphorylation and activation; p27Kip1, which forms a ternary complex with ASXL1 and AKT1, therefore remained unphosphorylated...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28698574/an-e2f1-mir-17-92-negative-feedback-loop-mediates-proliferation-of-mouse-palatal-mesenchymal-cells
#3
Ling Li, Bing Shi, Jin Chen, Chunhua Li, Shaoxin Wang, Zhaohui Wang, Guiquan Zhu
Normal cell cycle progression and proliferation of palatal mesenchymal cells are important for palatal development. As targets of miR-17-92, E2F transcription factors family has been suggested to induce the transcription of miR-17-92 in several cell types. In the present study, we sought to investigate whether this negative feedback loop exists in mouse PMCs and what the function of this negative feedback loop would be in palatal mesenchymal cells. Using GeneMANIA, we revealed that the most important function of experimentally verified targets of miR-17-92 is cell cycle regulation...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28698355/tissue-specific-control-of-the-endocycle-by-the-anaphase-promoting-complex-cyclosome-inhibitors-uvi4-and-del1
#4
Jefri Heyman, Stefanie Polyn, Thomas Eekhout, Lieven De Veylder
The endocycle represents a modified mitotic cell cycle that in plants is often coupled to cell enlargement and differentiation. Endocycle onset is controlled by activity of the Anaphase Promoting Complex/Cyclosome (APC/C), a multi-subunit E3 ubiquitin ligase targeting cell cycle factors for destruction. CELL CYCLE SWITCH 52 (CCS52) proteins represent rate-limiting activator subunits of the APC/C. In Arabidopsis thaliana (Arabidopsis), mutations in either CCS52A1 or CCS52A2 activators result in a delayed endocycle onset, whereas their overexpression triggers increased DNA ploidy levels...
July 11, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28677347/the-intersection-of-rb-tumor-suppressor-function-stem-cells-metabolism-and-inflammation
#5
REVIEW
Shunsuke Kitajima, Chiaki Takahashi
The RB tumor suppressor regulates the G1/S transition during cell cycle progression by modulating the activity of E2F transcription factors. The RB pathway plays a central role in the suppression of most of cancers, and RB mutation was initially discovered by virtue of its role in tumor initiation. However, as cancer genome sequencing has evolved to profile more advanced and treatment resistant cancers, it has become increasingly clear that in the majority of cancers somatic RB inactivation occurs during tumor progression...
July 5, 2017: Cancer Science
https://www.readbyqxmd.com/read/28667245/a-screen-for-inducers-of-bhlh-activity-identifies-pitavastatin-as-a-regulator-of-p21-rb-phosphorylation-and-e2f-target-gene-expression-in-pancreatic-cancer
#6
Nicholas Villarino, Lia Signaevskaia, Jaco van Niekerk, Rachel Medal, Heejung Kim, Reyhaneh Lahmy, Kathleen Scully, Anthony Pinkerton, SangWun Kim, Andrew Lowy, Pamela Itkin-Ansari
The average survival for patients with Pancreatic Ductal Adenocarcinoma (PDA) is merely 6 months, underscoring the need for new therapeutic approaches. During PDA progression, pancreatic acinar cells lose activity of the ClassI/II bHLH factors that regulate quiescence. We previously found that promoting transcriptional activity of the Class I bHLH factor E47 in highly aggressive PDA cells induced stable growth arrest in vitro and in vivo. To translate these findings for clinical utility, we developed a high throughput screening platform to identify small molecule inducers of Class I/II bHLH activity...
June 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28658208/recurrent-and-functional-regulatory-mutations-in-breast-cancer
#7
Esther Rheinbay, Prasanna Parasuraman, Jonna Grimsby, Grace Tiao, Jesse M Engreitz, Jaegil Kim, Michael S Lawrence, Amaro Taylor-Weiner, Sergio Rodriguez-Cuevas, Mara Rosenberg, Julian Hess, Chip Stewart, Yosef E Maruvka, Petar Stojanov, Maria L Cortes, Sara Seepo, Carrie Cibulskis, Adam Tracy, Trevor J Pugh, Jesse Lee, Zongli Zheng, Leif W Ellisen, A John Iafrate, Jesse S Boehm, Stacey B Gabriel, Matthew Meyerson, Todd R Golub, Jose Baselga, Alfredo Hidalgo-Miranda, Toshi Shioda, Andre Bernards, Eric S Lander, Gad Getz
Genomic analysis of tumours has led to the identification of hundreds of cancer genes on the basis of the presence of mutations in protein-coding regions. By contrast, much less is known about cancer-causing mutations in non-coding regions. Here we perform deep sequencing in 360 primary breast cancers and develop computational methods to identify significantly mutated promoters. Clear signals are found in the promoters of three genes. FOXA1, a known driver of hormone-receptor positive breast cancer, harbours a mutational hotspot in its promoter leading to overexpression through increased E2F binding...
July 6, 2017: Nature
https://www.readbyqxmd.com/read/28657656/functional-interrelationship-between-tfii-i-and-e2f-transcription-factors-at-specific-cell-cycle-gene-loci
#8
Yong Shen, Rukiye Nar, Alex Xiucheng Fan, Mahmoud Aryan, Mir A Hossain, Aishwarya Gurumurthy, Paul C Wassel, Ming Tang, Jianrong Lu, John Strouboulis, Jörg Bungert
Transcription factor TFII-I is a multifunctional protein implicated in the regulation of cell cycle and stress-response genes. Previous studies have shown that a subset of TFII-I associated genomic sites contained DNA-binding motifs for E2F family transcription factors. We analyzed the co-association of TFII-I and E2Fs in more detail using bioinformatics, chromatin immunoprecipitation, and co-immunoprecipitation experiments. The data show that TFII-I interacts with E2F transcription factors. Furthermore, TFII-I, E2F4, and E2F6 interact with DNA-regulatory elements of several genes implicated in the regulation of the cell cycle, including DNMT1, HDAC1, CDKN1C and CDC27...
June 28, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28650445/a-distinct-function-of-the-retinoblastoma-protein-in-the-control-of-lipid-composition-identified-by-lipidomic-profiling
#9
H Muranaka, A Hayashi, K Minami, S Kitajima, S Kohno, Y Nishimoto, N Nagatani, M Suzuki, L A N Kulathunga, N Sasaki, N Okada, T Matsuzaka, H Shimano, H Tada, C Takahashi
Here, by combining lipidomics with transcriptome analysis, we demonstrate that Rb depletion in mouse embryonic fibroblastss induces significant alterations in their lipid composition. We discovered that Rb depletion induced increase in lysophosphatidylserine, diacylglycerol (DAG), fatty acid (FA), acylcarnitine, phosphatidylcholine (PC), arachidonoyl ethanolamine, and decrease in phosphatidylglycerol, monoacylglycerol, without change in total lipid per protein levels. Analysis of the acyl chain composition of DAG, PC and phosphatidylserine revealed increase of saturated and mono-unsaturated acyl chains with specific carbon chain length...
June 26, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28649092/aryl-hydrocarbon-receptor-ahr-is-a-potential-tumour-suppressor-in-pituitary-adenomas
#10
Robert Formosa, Joseph Borg, Josanne Vassallo
Pituitary adenomas (PA) represent the largest group of intracranial neoplasms, yet the molecular mechanisms driving this disease remain largely unknown. The aim of this study was to use high-throughput screening to identify molecular pathways that may be playing a significant and consistent role in PA. RNA profiling using microarrays on eight local PAs identified the aryl hydrocarbon receptor (AHR) signalling pathway as a key canonical pathway down-regulated in all PA types. This was confirmed by qPCR in 31 tumours...
June 25, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28638310/analysis-of-gene-expression-in-human-dermal-fibroblasts-treated-with-senescence-modulating-cox-inhibitors
#11
Jeong A Han, Jong-Il Kim
We have previously reported that NS-398, a cyclooxygenase-2 (COX-2)-selective inhibitor, inhibited replicative cellular senescence in human dermal fibroblasts and skin aging in hairless mice. In contrast, celecoxib, another COX-2-selective inhibitor, and aspirin, a non-selective COX inhibitor, accelerated the senescence and aging. To figure out causal factors for the senescence-modulating effect of the inhibitors, we here performed cDNA microarray experiment and subsequent Gene Set Enrichment Analysis. The data showed that several senescence-related gene sets were regulated by the inhibitor treatment...
June 2017: Genomics & Informatics
https://www.readbyqxmd.com/read/28634077/depdc1-promotes-cell-proliferation-and-tumor-growth-via-activation-of-e2f-signaling-in-prostate-cancer
#12
Lin Huang, Keng Chen, Zhao-Peng Cai, Fu-Chao Chen, Hui-Yong Shen, Wei-Hua Zhao, Song-Jie Yang, Xu-Biao Chen, Guo-Xue Tang, Xi Lin
DEP domain containing 1 (DEPDC1) is recently reported to be overexpressed in several types of human cancer; however the role of DEPDC1 in prostate cancer remains to be investigated. Herein, we identified that the DEPDC1 mRNA and protein expression levels were dramatically increased in prostate cancer tissues and cell lines. Overexpression of DEPDC1 promoted, but depletion of DEPDC1 inhibited cell proliferation by regulating the G1-S phase cell cycle transition. Importantly, we found that DEPDC1 was essential for the tumor growth and formation of bone metastases of prostate cancer cells in vivo...
June 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28620137/biological-specificity-of-cdk4-6-inhibitors-dose-response-relationship-in-vivo-signaling-and-composite-response-signature
#13
Erik S Knudsen, Jack Hutcheson, Paris Vail, Agnieszka K Witkiewicz
Recently developed potent and selective CDK4/6 inhibitors fall into two classes based on structure and toxicity profiles in clinical studies. One class, exemplified by palbociclib and ribociclib, exhibits neutropenia as a dose-limiting toxicity and requires discontinuous dosing. In contrast, the structurally distinct CDK4/6 inhibitor abemaciclib is dosed continuously, and has diarrhea and fatigue as dose-limiting toxicities. In preclinical models, palbociclib has been extensively studied and induces cell cycle inhibition in an RB-dependent manner...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28614707/linker-histone-h1-2-directs-genome-wide-chromatin-association-of-the-retinoblastoma-tumor-suppressor-protein-and-facilitates-its-function
#14
Shonagh Munro, Edward S Hookway, Melanie Floderer, Simon M Carr, Rebecca Konietzny, Benedikt M Kessler, Udo Oppermann, Nicholas B La Thangue
The retinoblastoma tumor suppressor protein pRb is a master regulator of cellular proliferation, principally through interaction with E2F and regulation of E2F target genes. Here, we describe the H1.2 linker histone as a major pRb interaction partner. We establish that H1.2 and pRb are found in a chromatin-bound complex on diverse E2F target genes. Interrogating the global influence of H1.2 on the genome-wide distribution of pRb indicated that the E2F target genes affected by H1.2 are functionally linked to cell-cycle control, consistent with the ability of H1...
June 13, 2017: Cell Reports
https://www.readbyqxmd.com/read/28612064/e2f-site-in-the-essential-promoter-region-does-not-confer-s-phase-specific-transcription-of-the-abcc10-gene-in-human-prostate-cancer-cells
#15
Magdalena Dabrowska, Francis M Sirotnak
ABCC10 (MRP7) plays a role in cellular detoxification and resistance to anticancer drugs. Since ABCC10 gene transcription in human prostate cancer CWR22Rv1 cells was found dependent on E2F binding sequence motif, ABCC10 expression in G1 and S phases of the cell cycle of CWR22Rv1 cells, was analyzed. The cells were synchronized in G1 phase by double thymidine block and in S phase by thymidine/mimosine double block. ABCC10 mRNA level was found to be similar in S phase-synchronized and asynchronous cell populations...
2017: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/28610850/dietary-myo-inositol-deficiency-decreased-the-growth-performances-and-impaired-intestinal-physical-barrier-function-partly-relating-to-nrf2-jnk-e2f4-and-mlck-signaling-in-young-grass-carp-ctenopharyngodon-idella
#16
Shuang-An Li, Wei-Dan Jiang, Lin Feng, Yang Liu, Pei Wu, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Xu Tang, He-Qun Shi, Xiao-Qiu Zhou
In this study, we investigated the effects of dietary myo-inositol on the growth and intestinal physical barrier functions of young grass carp (Ctenopharyngodon idella). A total of 540 young grass carp (221.83 ± 0.84 g) were fed six diets containing graded levels of myo-inositol (27.0, 137.9, 286.8, 438.6, 587.7 and 737.3 mg/kg) for 10 weeks. After the growth trial, fish were challenged with Aeromonas hydrophila for 14 days. The results indicated that compared with optimal myo-inositol levels, myo-inositol deficiency (27...
August 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28607595/e2f8-is-a-potential-therapeutic-target-for-hepatocellular-carcinoma
#17
REVIEW
Yi Lv, Jia Xiao, Jing Liu, Feiyue Xing
E2F transcriptional factors are widely expressed in a number of tissues and organs, possessing many regulatory functions related to cellular proliferation, differentiation, DNA repair, cell-cycle and cell apoptosis. E2F8 is a recently identified member of the E2F family with a duplicated DNA-binding domain feature discriminated from E2F1-6, controlling gene expression in a dimerization partner-independent manner. It is indispensable for angiogenesis, lymphangiogenesis and embryonic development. Although E2F8 and E2F7 perform complementary and overlapping functions in many cell metabolisms, E2F8, but not E2F7, overexpresses remarkably in hepatocellular carcinoma (HCC) to facilitate the HCC occurrence and development via activating a E2F1/ Cyclin D1 signaling pathway to regulate the G1- to S-phase transition of cell cycle progression or transcriptionally suppressing CDK1 to induce hepatocyte polyploidization...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28600888/homeostatic-control-of-start-through-negative-feedback-between-cln3-cdk1-and-rim15-greatwall-kinase-in-budding-yeast
#18
Nicolas Talarek, Elisabeth Gueydon, Etienne Schwob
How cells coordinate growth and division is key for size homeostasis. Phosphorylation by G1-CDK of Whi5/Rb inhibitors of SBF/E2F transcription factors triggers irreversible S-phase entry in yeast and metazoans, but why this occurs at a given cell size is not fully understood. We show that the yeast Rim15-Igo1,2 pathway, orthologous to Gwl-Arpp19/ENSA, is up-regulated in early G1 and helps promoting START by preventing PP2A(Cdc55) to dephosphorylate Whi5. RIM15 overexpression lowers cell size while IGO1,2 deletion delays START in cells with low CDK activity...
June 10, 2017: ELife
https://www.readbyqxmd.com/read/28599485/mirna-34a-enhances-the-sensitivity-of-gastric-cancer-cells-to-treatment-with-paclitaxel-by-targeting-e2f5
#19
Lina Li, Cuiling Wu, Yue Zhao
Gastric cancer (GC) is one of the most common types of malignant cancer worldwide, however improvements are required to the current therapies for GC. Although paclitaxel is one of the most promising chemotherapeutic agents in clinical use for GC, the resistance to paclitaxel that develops during treatment is a major obstacle to further treatments of GC. The present study reports that micro (mi) RNA-34a, a tumor suppressor in various types of cancer, may be an important regulator of chemoresistance in GC, as miRNA-34a mimics and inhibitors, enhance and inhibit the chemotherapeutic efficacy of paclitaxel, respectively...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28596493/upregulation-of-long-noncoding-rna-hoxa-as3-promotes-tumor-progression-and-predicts-poor-prognosis-in-glioma
#20
Fan Wu, Chuanbao Zhang, Jinquan Cai, Fan Yang, Tingyu Liang, Xiaoyan Yan, Haoyuan Wang, Wen Wang, Jing Chen, Tao Jiang
Long noncoding RNAs (lncRNAs) have recently emerged as new potentially promising therapeutic targets in many cancers. However, their prognostic value and biological functions associated with glioma remain to be elucidated. Here, High-throughput RNAseq was performed to detect the expression profiles of lncRNAs in 325 human glioma tissues. It was shown that a novel lncRNA HOXA-AS3 was one of the most significantly upregulated lncRNAs in glioma tissues. Quantitative PCR further verified the increased expression of HOXA-AS3 in patient samples and glioma cell lines...
May 24, 2017: Oncotarget
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