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https://www.readbyqxmd.com/read/28754531/carf-is-a-multi-module-regulator-of-cell-proliferation-and-a-molecular-bridge-between-cellular-senescence-and-carcinogenesis
#1
REVIEW
Renu Wadhwa, Rajkumar Singh Kalra, Sunil C Kaul
CARF (Collaborator of ARF) was first identified as an ARF (Alternative Reading Frame, p14ARF)-interacting protein in a yeast two-hybrid interactive screening. Subsequently, it was shown to stabilize the p53-tumor suppressor protein in an ARF-dependent or -independent manner. It acts as a transcriptional repressor of HDM2 that exerts a negative feedback on p53 by its proteasomal-mediated degradation. CARF-driven control over p53-HDM2-p21(WAF1) axis was shown to regulate cell proliferative fates. Cells with CARF-overexpression (CARF-OE) and superexpression (CARF-SE) showed growth arrest and pro-proliferative phenotypes, respectively...
July 25, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28711940/clinical-significance-of-p16ink4a-and-p14arf-promoter-methylation-in-renal-cell-carcinoma-a-meta-analysis
#2
Yu Ren, Li Xiao, Guobin Weng, Bingyi Shi
The inactivation of p16INK4A and p14ARF via promoter methylation has been investigated in various cancers. However, the clinical effects of p16INK4A and p14ARF promoter methylation on renal cell carcinoma (RCC) remain to be clarified. The pooled data were calculated and summarized. Finally, an investigation of 14 eligible studies with 1231 RCC patients and 689 control patients was performed. Methylated p16INK4A and p14ARF were observed to be significantly higher in RCC than in control subjects without malignancies (OR = 2...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28529622/ires-mediated-protein-translation-overcomes-suppression-by-the-p14arf-tumor-suppressor-protein
#3
Song Xi, Ming Zhao, Si Wang, Ling Ma, Shensen Wang, Xianling Cong, Ruth A Gjerset, Rebecca C Fitzgerald, Yinghui Huang
Internal ribosome entry sites (IRES elements) have attracted interest in cancer gene therapy because they can be used in the design of gene transfer vectors that provide bicistronic co-expression of two transgene products under the control of a single promoter. Unlike cellular translation of most mRNAs, a process that requires a post-translational 5' modification of the mRNA known as the cap structure, IRES-mediated translation is independent of the cap structure. The cellular conditions that may intervene to modulate IRES-mediated, cap-independent versus cap-dependent translation, however, remain poorly understood, although they could be critical to the choice of gene transfer vectors...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28436949/p14arf-interacts-with-the-focal-adhesion-kinase-and-protects-cells-from-anoikis
#4
M Vivo, R Fontana, M Ranieri, G Capasso, T Angrisano, A Pollice, V Calabrò, G La Mantia
The ARF protein functions as an important sensor of hyper-proliferative stimuli restricting cell proliferation through both p53-dependent and -independent pathways. Although to date the majority of studies on ARF have focused on its anti-proliferative role, few studies have addressed whether ARF may also have pro-survival functions. Here we show for the first time that during the process of adhesion and spreading ARF re-localizes to sites of active actin polymerization and to focal adhesion points where it interacts with the phosphorylated focal adhesion kinase...
August 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28431405/usp5-functions-as-an-oncogene-for-stimulating-tumorigenesis-in-hepatocellular-carcinoma
#5
Yi Liu, Wei-Mao Wang, Ying-Fei Lu, Lu Feng, Li Li, Ming-Zhu Pan, Yu Sun, Chun-Wai Suen, Wei Guo, Jian-Xin Pang, Jin-Fang Zhang, Wei-Ming Fu
As deubiquitinases, several ubiquitin specific protease members have been reported to mediate tumorigenesis. Although ubiquitin specific protease 5 (Usp5) was previously demonstrated to suppress p53 transcriptional activity and DNA repair, its role in carcinogenesis remains elusive. In this study, we sought to define a novel role of Usp5 in tumorigenesis. It was found that Usp5 was significantly upregulated in hepatocellular carcinoma (HCC) cells and most clinical specimens. Further functional investigation also showed that Usp5 knockdown suppressed cell proliferation, migration, drug resistance and induced apoptosis; on the other hand, Usp5 overexpression promoted colony formation, migration, drug resistance and tumorigenesis...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28265066/resistance-mechanisms-to-tp53-mdm2-inhibition-identified-by-in-vivo-piggybac-transposon-mutagenesis-screen-in-an-arf-mouse-model
#6
Emilie A Chapeau, Agnieszka Gembarska, Eric Y Durand, Emeline Mandon, Claire Estadieu, Vincent Romanet, Marion Wiesmann, Ralph Tiedt, Joseph Lehar, Antoine de Weck, Roland Rad, Louise Barys, Sebastien Jeay, Stephane Ferretti, Audrey Kauffmann, Esther Sutter, Armelle Grevot, Pierre Moulin, Masato Murakami, William R Sellers, Francesco Hofmann, Michael Rugaard Jensen
Inhibitors of double minute 2 protein (MDM2)-tumor protein 53 (TP53) interaction are predicted to be effective in tumors in which the TP53 gene is wild type, by preventing TP53 protein degradation. One such setting is represented by the frequent CDKN2A deletion in human cancer that, through inactivation of p14ARF, activates MDM2 protein, which in turn degrades TP53 tumor suppressor. Here we used piggyBac (PB) transposon insertional mutagenesis to anticipate resistance mechanisms occurring during treatment with the MDM2-TP53 inhibitor HDM201...
March 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28193319/a-conformational-switch-regulates-the-ubiquitin-ligase-huwe1
#7
Bodo Sander, Wenshan Xu, Martin Eilers, Nikita Popov, Sonja Lorenz
The human ubiquitin ligase HUWE1 has key roles in tumorigenesis, yet it is unkown how its activity is regulated. We present the crystal structure of a C-terminal part of HUWE1, including the catalytic domain, and reveal an asymmetric auto-inhibited dimer. We show that HUWE1 dimerizes in solution and self-associates in cells, and that both occurs through the crystallographic dimer interface. We demonstrate that HUWE1 is inhibited in cells and that it can be activated by disruption of the dimer interface. We identify a conserved segment in HUWE1 that counteracts dimer formation by associating with the dimerization region intramolecularly...
February 14, 2017: ELife
https://www.readbyqxmd.com/read/28185908/purification-and-biophysical-characterization-of-the-aimp2-dx2-protein
#8
Roshan Jha, Hye Young Cho, Ameeq Ul Mushtaq, Kiho Lee, Dae Gyu Kim, Sunghoon Kim, Young Ho Jeon
Besides their primary role in protein synthesis, aminoacyl-tRNA synthetases (AARSs) are involved in several non-canonical processes such as apoptosis, inflammation and angiogenesis through their interactions with various cellular proteins. Nine of these AARSs interact with three aminoacyl-tRNA synthetase interacting multifunctional proteins (AIMPs), forming a multi-synthetase complex (MSC) in eukaryotes. Among the three AIMPs, AIMP2 is involved in controlling cell proliferation and apoptosis. However, a splicing variant of AIMP2 lacking exon 2, referred to as AIMP2-DX2, is oncogenic and compromises the pro-apoptotic activity of AIMP2 by competing with it for p53 and TRAF2...
April 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28150872/polymorphism-in-anril-is-associated-with-relapse-in-patients-with-multiple-myeloma-after-autologous-stem-cell-transplant
#9
Ming J Poi, Junan Li, Douglas W Sborov, Zachary VanGundy, Yu Kyoung Cho, Misty Lamprecht, Flavia Pichiorri, Mitch A Phelps, Craig C Hofmeister
Multiple myeloma (MM) is a hematologic malignancy characterized by clonal proliferation of plasma cells and overproduction of monoclonal immunoglobins. Treatment with melphalan is currently standard of care for younger and fit patients when followed by hematopoietic stem cell transplantation (HSCT), and in transplant ineligible patients when used in combination regimens. It has been previously shown that changes in the p53 pathway are associated with melphalan efficacy, but the regulatory role of the p14ARF-MDM2-p53 axis has yet to be fully explored...
February 2, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28068434/annexin-s100a-protein-family-regulation-through-p14arf-p53-activation-a-role-in-cell-survival-and-predicting-treatment-outcomes-in-breast-cancer
#10
Diana Hatoum, Daniel Yagoub, Alireza Ahadi, Najah T Nassif, Eileen M McGowan
The annexin family and S100A associated proteins are important regulators of diverse calcium-dependent cellular processes including cell division, growth regulation and apoptosis. Dysfunction of individual annexin and S100A proteins is associated with cancer progression, metastasis and cancer drug resistance. This manuscript describes the novel finding of differential regulation of the annexin and S100A family of proteins by activation of p53 in breast cancer cells. Additionally, the observed differential regulation is found to be beneficial to the survival of breast cancer cells and to influence treatment efficacy...
2017: PloS One
https://www.readbyqxmd.com/read/27997910/effects-of-cdkn2a-p16ink4a-p14arf-over-expression-on-proliferation-and-migration-of-human-melanoma-a375-cells
#11
Ming Bai, Nan-Ze Yu, Fei Long, Cheng Feng, Xiao-Jun Wang
OBJECTIVE: This study aims to investigate the effects of CDKN2A (p16INK4A/p14ARF) over-expression on the proliferation and migration of human melanoma A375 cells. METHODS: Melanoma tissues and pigmented nevi tissues were collected. Human melanoma A375 cells were transfected by CDKN2A (p16INK4A) and CDKN2A (p14ARF) over-expressing vectors and then assigned into blank, negative control (NC), p16INK4A and p14ARF groups. The expression of CDKN2A (p16INK4A) and CDKN2A (p14ARF) mRNA and protein was detected by qRT-PCR and Western blotting...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27965321/suppressing-p16-ink4a-and-p14-arf-pathways-overcomes-apoptosis-in-individualized-human-embryonic-stem-cells
#12
Wenqian Wang, Yanling Zhu, Ke Huang, Yongli Shan, Juan Du, Xiaoya Dong, Ping Ma, Penafei Wu, Jian Zhang, Wenhao Huang, Tian Zhang, Baojian Liao, Deyang Yao, Guangjin Pan, Jiajun Liu
Dissociation-induced apoptosis is a striking phenomenon in human embryonic stem cells (hESCs), but not in naive mouse ESCs. Rho-associated kinase-dependent actin-myosin hyperactivation is an underlying mechanism that triggers apoptosis in dissociated hESCs; however, in this study, we show that the Ink4A-ARF-mediated senescence pathway is another mechanism to cause apoptosis in individualized hESCs. We show that P16(INK4A) and P14(ARF) are immediately induced in hESCs upon dissociation, but not in mouse ESCs...
March 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27814275/detection-of-bladder-cancer-in-urine-sediments-by-a-hypermethylation-panel-of-selected-tumor-suppressor-genes
#13
Michaƚ Pietrusiński, Ƚukasz Kȩpczyński, Adam Jȩdrzejczyk, Edyta Borkowska, Magdalena Traczyk-Borszyńska, Maria Constantinou, Bogdan Kaƚużewski, Maciej Borowiec
BACKGROUND: Promoter hypermethylation can be a useful biomarker for early detection and prognosis of bladder cancer, monitoring response to treatment and complement classical diagnostic procedures. OBJECTIVE: The molecular test was performed on DNA from bladder cancer cells in voided urine samples, tumor tissue DNA and normal control DNAs. We aimed to assess the diagnostic potential of epigenetic changes in urine DNA from bladder cancer cases at various clinico-pathological stages of the disease...
2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/27793846/molecular-chaperone-hsp90-is-necessary-to-prevent-cellular-senescence-via-lysosomal-degradation-of-p14arf
#14
Su Yeon Han, Aram Ko, Haruhisa Kitano, Chel Hun Choi, Min-Sik Lee, Jinho Seo, Junya Fukuoka, Soo-Youl Kim, Stephen M Hewitt, Joon-Yong Chung, Jaewhan Song
The tumor suppressor function of p14ARF is regulated at a posttranslational level via mechanisms yet to be fully understood. Here, we report the identification of an unconventional p14ARF degradation pathway induced by the chaperone HSP90 in association with the E3 ubiquitin ligase C-terminus of HSP70-interacting protein (CHIP). The ternary complex of HSP90, CHIP, and p14ARF was required to induce the lysosomal degradation of p14ARF by an ubiquitination-independent but LAMP2A-dependent mechanism. Depletion of HSP90 or CHIP induced p14ARF-dependent senescence in human fibroblasts...
January 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/27507052/long-non-coding-rna-anril-promotes-the-invasion-and-metastasis-of-thyroid-cancer-cells-through-tgf-%C3%AE-smad-signaling-pathway
#15
Jian-Jie Zhao, Shuai Hao, Ling-Li Wang, Chun-Yan Hu, Shu Zhang, Ling-Ji Guo, Gang Zhang, Bo Gao, Yan Jiang, Wu-Guo Tian, Dong-Lin Luo
OBJECTIVE: To investigate the effect of antisense non-coding RNA in the INK4 locus (ANRIL) on invasion and metastasis of thyroid cancer (TC). RESULTS: ANRIL expression was significantly up-regulated in TC tissues and cells (P < 0.001), and ANRIL expression was significantly different regarding histological grade and LNM (both P < 0.01). The siRNA-mediated ANRIL silencing inhibits proliferation, invasion, and metastasis of TPC-1 and SW579 cells, and lung metastasis, which can be reversed by TGF-β1 siRNA...
September 6, 2016: Oncotarget
https://www.readbyqxmd.com/read/27436753/k259-sumoylation-of-dgcr8-promoted-by-p14arf-exerts-a-tumor-suppressive-function
#16
Changhong Zhu, Cheng Chen, Ran Chen, Rong Deng, Xian Zhao, Hailong Zhang, Jinzhuo Duo, Qin Chen, Hui Jin, Yanli Wang, Jian Huang, Ming Xu, Jianxiu Yu
No abstract text is available yet for this article.
July 19, 2016: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27414035/genetic-variants-in-the-p14arf-mdm2-tp53-pathway-are-associated-with-the-prognosis-of-esophageal-squamous-cell-carcinoma-patients-treated-with-radical-resection
#17
Jing Li, Yang Tang, Liu Huang, Qianqian Yu, Guangyuan Hu, Xianglin Yuan
The p14ARF/MDM2/ TP53 pathway is known to play an important role in tumor progression by cell cycle control, although the association between this pathway and the prognosis of esophageal squamous cell carcinoma (ESCC) is unclear. In this study, we explored the association between genetic variants in the p14ARF/MDM2/TP53 pathway and prognosis in ESCC patients with radical resection. 124 ESCC patients with radical resection were included in this retrospective study and genotyped using the MassArray method. According to multivariate Cox hazard analysis and multiple testing, the TC/CC genotype of p14ARF rs3814960 was shown to be strongly related to a decreased overall survival (OS) (HR = 2...
2016: PloS One
https://www.readbyqxmd.com/read/27356775/the-9p21-locus-and-its-potential-role-in-atherosclerosis-susceptibility-molecular-mechanisms-and-clinical-implications
#18
Amir Tajbakhsh, Seyed Mahdi Hassanian, Mohammad Sadegh Khorrami, Alireza Pasdar, Ehsan Tabatabai, Seyed Mohammad Reza Parizadeh, Mostafa Fazeli, Sharareh Gholamin, Gordon A Ferns, Majid Ghayour-Mobarhan, Amir Avan
Cardiovascular disease (CVD) is the leading cause of global mortality. Although extensive efforts have been made to identify valid biomarkers for CVD risk, relatively ¬¬¬few are of proven clinical utility. It is recognized that genetic factors play a major role in determining the susceptibility to CVD. Recent genome-wide-association-studies have demonstrated common genetic variants in a region on chromosome 9p21 associated with an increased risk of CVD. Several genetic-polymorphisms have been identified in this region that are highly associated with CVD, and these are clustered around the gene loci for CDKN2B (coding for p15ink4b), CDKN2A (coding for p16ink4a and p14ARF) and the 3' end of CDKN2BAS, which has been termed antisense noncoding RNA in the INK4 locus (ANRIL)...
June 27, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27356744/mmp7-interacts-with-arf-in-nucleus-to-potentiate-tumor-microenvironments-for-prostate-cancer-progression-in-vivo
#19
Yingqiu Xie, Wenfu Lu, Shenji Liu, Qing Yang, J Shawn Goodwin, Sandeep Anantha Sathyanarayana, Siddharth Pratap, Zhenbang Chen
ARF couples with TP53 in a canonical signaling pathway to activate cellular senescence for tumor suppressive function under oncogenic insults. However, the mechanisms on aberrant elevation of ARF in cancers are still poorly understood. We previously showed that ARF (p14ARF in human and p19Arf in mouse) elevation correlates with PTEN loss and stabilizes SLUG to reduce cell adhesion in prostate cancer (PCa). Here we report that ARF is essential for MMP7 expression, E-Cadherin decrease and the anchorage loss to the extracellular matrix (ECM) in PCa in vitro and in vivo...
July 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27323397/gltscr2-promotes-the-nucleoplasmic-translocation-and-subsequent-degradation-of-nucleolar-arf
#20
Sun Lee, Young-Eun Cho, Sang-Hoon Kim, Yong-Jun Kim, Jae-Hoon Park
The alternative reading frame protein (p14ARF/ARF) is a key determinant of cell fate, acting as a potent tumor suppressor through a p53/MDM2-dependent pathway or promoting apoptosis in a p53-independent manner. The ARF protein is mainly expressed in the nucleolus and sequestered by nucleophosmin (NPM), whereas ARF-binding proteins, including p53 and MDM2, predominantly reside in the nucleoplasm. This raises the question of how nucleolar ARF binds nucleoplasmic signaling proteins to suppress tumor growth or inhibit cell cycle progression...
March 7, 2017: Oncotarget
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