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https://www.readbyqxmd.com/read/29352246/u-box-ubiquitin-ligase-ppil2-suppresses-breast-cancer-invasion-and-metastasis-by-altering-cell-morphology-and-promoting-snai1-ubiquitination-and-degradation
#1
Zhaojun Jia, Miao Wang, Shujing Li, Xiahui Li, Xiao-Yan Bai, Zhaowei Xu, Yangyang Yang, Bowen Li, Yanan Li, Huijian Wu
Metastasis is the leading cause of breast cancer fatalities. To develop new therapeutic strategies, the mechanisms underlying breast cancer invasion and metastasis need to be further investigated. Peptidylprolyl isomerase (cyclophilin)-like 2 (PPIL2) is a U-box-type E3 ubiquitin ligase belonging to the cyclophilin family. Proteins within this family are the major cytosolic binding proteins of the immunosuppressant drug cyclosporine A (CsA). Although PPIL2 has been reported to potentially be involved in cell migration, its role in breast cancer is still unclear...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29350614/lipg-signaling-promotes-tumor-initiation-and-metastasis-of-human-basal-like-triple-negative-breast-cancer
#2
Pang-Kuo Lo, Yuan Yao, Ji Shin Lee, Yongshu Zhang, Weiliang Huang, Maureen A Kane, Qun Zhou
Current understanding of aggressive human basal-like triple-negative breast cancer (TNBC) remains incomplete. In this study, we show endothelial lipase (LIPG) is aberrantly overexpressed in basal-like TNBCs. We demonstrate that LIPG is required for in vivo tumorigenicity and metastasis of TNBC cells. LIPG possesses a lipase-dependent function that supports cancer cell proliferation and a lipase-independent function that promotes invasiveness, stemness and basal/epithelial-mesenchymal transition features of TNBC...
January 19, 2018: ELife
https://www.readbyqxmd.com/read/29349575/parkin-in-parkinson-s-disease-and-cancer-a-double-edged-sword
#3
REVIEW
Khushnuma Wahabi, Ahmad Perwez, Moshahid A Rizvi
Parkin for more than a decade has been portrayed as a neuroprotector gene is now increasingly emerging as a multifaceted gene that can exert entirely opposite effects i.e., both cell proliferation and apoptosis. Parkinson's disease, a neurological disease, progresses due to excess in cell death, while, in case of cancer, cell death normally fails to occur. Parkin, an E3 ubiquitin ligase, was first identified as a gene implicated in autosomal recessive juvenile Parkinsonism, but several evidences indicate that Parkin is a tumor suppressor gene, involved in a variety of cancers...
January 18, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29348847/distinct-roles-of-traf6-and-tak1-in-the-regulation-of-adipocyte-survival-thermogenesis-program-and-high-fat-diet-induced-obesity
#4
Yann S Gallot, Joseph D McMillan, Guangyan Xiong, Kyle R Bohnert, Alex R Straughn, Bradford G Hill, Ashok Kumar
Chronic low-grade inflammation, adipocyte hypertrophy, and glucose intolerance are common features of obesity and a risk factor for cancer. Tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) is an adaptor protein that also possesses a non-conventional E3 ubiquitin ligase activity. In response to receptor-mediated events, TRAF6 activates transforming growth factor-activated kinase 1 (TAK1), which leads to activation of the MAPK and nuclear factor-kappa B (NF-κB) signaling pathways. However, the roles of TRAF6 and TAK1 in the regulation of adipocyte function remain less understood...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348145/fbxl13-directs-the-proteolysis-of-cep192-to-regulate-centrosome-homeostasis-and-cell-migration
#5
Ella Fung, Carmen Richter, Hong-Bin Yang, Isabell Schäffer, Roman Fischer, Benedikt M Kessler, Florian Bassermann, Vincenzo D'Angiolella
Aberrant centrosome organisation with ensuing alterations of microtubule nucleation capacity enables tumour cells to proliferate and invade despite increased genomic instability. CEP192 is a key factor in the initiation process of centrosome duplication and in the control of centrosome microtubule nucleation. However, regulatory means of CEP192 have remained unknown. Here, we report that FBXL13, a binding determinant of SCF (SKP1-CUL1-F-box)-family E3 ubiquitin ligases, is enriched at centrosomes and interacts with the centrosomal proteins Centrin-2, Centrin-3, CEP152 and CEP192...
January 18, 2018: EMBO Reports
https://www.readbyqxmd.com/read/29346004/universal-lead-screening-requirement-a-california-case-study
#6
Sara B McMenamin, Sarah P Hiller, Erin Shigekawa, Troy Melander, Riti Shimkhada
OBJECTIVES: To estimate potential impacts of California Assembly Bill (AB) 1316: a requirement for universal screening and insurance coverage for child blood lead testing. METHODS: In April 2017 the California Health Benefits Review Program (Oakland, CA) analyzed AB 1316 for the California legislature, including a systematic review of lead screening effectiveness, commercial insurer surveys regarding screening coverage, and actuarial utilization and cost implication assessments...
January 18, 2018: American Journal of Public Health
https://www.readbyqxmd.com/read/29346003/medicaid-expansion-and-infant-mortality-in-the-united-states
#7
Chintan B Bhatt, Consuelo M Beck-Sagué
OBJECTIVES: To explore the effect of Medicaid expansion on US infant mortality rate. METHODS: We examined data from 2010 to 2016 and 2014 to 2016 to compare infant mortality rates in states and Washington, DC, that accepted the Affordable Care Act Medicaid expansion (Medicaid expansion states) and states that did not (non-Medicaid expansion states), stratifying data by race/ethnicity. RESULTS: Mean infant mortality rate in non-Medicaid expansion states rose (6...
January 18, 2018: American Journal of Public Health
https://www.readbyqxmd.com/read/29346000/preventable-emergency-department-visits-for-nontraumatic-dental-conditions-trends-and-disparities-in-nevada-2009-2015
#8
Wenlian Zhou, Pearl Kim, Jay J Shen, Joseph Greenway, Marcia Ditmyer
OBJECTIVES: To examine trends and socioeconomic disparities for preventable dental-related emergency department (ED) visits in Nevada. METHODS: We pooled retrospective data containing 66 267 ED visits involving dental conditions from Nevada hospital ED databases from 2009 to 2015. The dependent variable was nontraumatic dental conditions identified by International Classification of Diseases, Ninth Revision, codes; 3 independent variables included treatment year, health insurance status, and race/ethnicity...
January 18, 2018: American Journal of Public Health
https://www.readbyqxmd.com/read/29345925/catalytic-mechanism-of-the-ubiquitin-like-nedd8-transfer-in-ring-e3-e2-nedd8-target-complex-from-qm-mm-free-energy-simulations
#9
Yufei Yue, Yue Ma, Ping Qian, Hong Guo
Ubiquitin-like (UBL) protein modifications play a key role in regulating protein function. In contrast to the ubiquitin (UB) and small ubiquitin-like modifier (SUMO) which are ligated to a massive segment of proteome, the UBL NEDD8 is highly selective for modifying a lysine residue on closely related cullin proteins (CULs). In this study, the X-ray structure of a trapped E3-E2~NEDD8-target intermediate (RBX1-UBC1~NEDD8-CUL1-DCN1) is used to build computer models, and combined quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) and free energy (potential of mean force) simulations are performed to investigate the catalytic mechanism of the NEDD8 transfer from E2 to the lysine residue (K720) on the substrate in the complex...
January 18, 2018: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29344247/upregulation-of-the-checkpoint-protein-chfr-is-associated-with-tumor-suppression-in-pancreatic-cancers
#10
Di Zhang, Xiao-Lan Xu, Fei Li, Hai-Chen Sun, Ye-Qing Cui, Shuang Liu, Ping-Yong Xu
The checkpoint with forkhead-associated (FHA) domain and RING-finger (CHFR) protein was identified as a cell cycle checkpoint protein and E3 ubiquitin ligase. In the present study, the potential functions of CHFR in pancreatic cancer were investigated. CHFR expression was measured in five pancreatic cancer cell lines by reverse transcription- quantitative polymerase chain reaction and western blotting. Capan-1 cells stably expressing CHFR were established by lentiviral vector transfection. Cell proliferation was assessed using Cell Counting Kit-8, and cell migration/invasion assay was determined using Transwell assays...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344143/function-of-cell-cycle-regulators-in-predicting-silent-pituitary-adenoma-progression-following-surgical-resection
#11
Sung Hyun Park, Ji Hwan Jang, Young Min Lee, Joon Soo Kim, Kyu Hong Kim, Young Zoon Kim
The present study investigated the use of cell-cycle regulators for predicting the progression of silent pituitary adenoma (SPA) following surgical resection, via immunohistochemical analysis of tumor samples obtained by surgical resection. The medical records of patients diagnosed with SPA between January 2000 and December 2013 in the Samsung Changwon Hospital, Sungkyunkwan University School of Medicine (Changwon, South Korea) were reviewed. Immunohistochemical staining was performed on sections of the archived, paraffin-embedded tissues obtained by surgery, with all tissues stained for cell-cycle regulatory proteins p16, p15, p21, cyclin-dependent kinase (CDK)4, CDK6, retinoblastoma protein (pRb) and cyclin D1, as well as E3 ubiquitin-protein ligase mib1 (MIB-1) antigen and p53...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343851/ndrg2-facilitates-colorectal-cancer-differentiation-through-the-regulation-of-skp2-p21-p27-axis
#12
Liangliang Shen, Xuan Qu, Huichen Li, Chunsheng Xu, Mengying Wei, Qinhao Wang, Yi Ru, Bei Liu, Yuqiao Xu, Kai Li, Junbi Hu, Lifeng Wang, Yongzheng Ma, Mengyang Li, Xiaofeng Lai, Lei Gao, Kaichun Wu, Libo Yao, Jianyong Zheng, Jian Zhang
Poorly differentiated colorectal cancers (CRCs) are more aggressive and lack targeted therapies. We and others previously reported the predominant role of tumor-suppressor NDRG2 in promoting CRC differentiation, but the underlying mechanism is largely unknown. Herein, we demonstrate that NDRG2 induction of CRC cell differentiation is dependent on the repression of E3 ligase Skp2 activity. In patients and Ndrg2 knockout mice, NDRG2 and Skp2 are negatively correlated and associated with cell differentiation stage...
January 18, 2018: Oncogene
https://www.readbyqxmd.com/read/29343848/a-novel-protein-encoded-by-the-circular-form-of-the-shprh-gene-suppresses-glioma-tumorigenesis
#13
Maolei Zhang, Nunu Huang, Xuesong Yang, Jingyan Luo, Sheng Yan, Feizhe Xiao, Wenping Chen, Xinya Gao, Kun Zhao, Huangkai Zhou, Ziqiang Li, Liu Ming, Bo Xie, Nu Zhang
Circular RNAs (circRNAs) are recognized as functional non-coding transcripts in eukaryotic cells. Recent evidence has indicated that even though circRNAs are generally expressed at low levels, they may be involved in many physiological or pathological processes, such as gene regulation, tissue development and carcinogenesis. Although the 'microRNA sponge' function is well characterized, most circRNAs do not contain perfect trapping sites for microRNAs, which suggests the possibility that circRNAs have functions that have not yet been defined...
January 18, 2018: Oncogene
https://www.readbyqxmd.com/read/29343641/degradation-of-fbxo31-by-apc-c-is-regulated-by-akt-and-atm-mediated-phosphorylation
#14
Srinadh Choppara, Sunil K Malonia, Ganga Sankaran, Michael R Green, Manas Kumar Santra
The F-box protein FBXO31 is a tumor suppressor that is encoded in 16q24.3, for which there is loss of heterozygosity in various solid tumors. FBXO31 serves as the substrate-recognition component of the SKP/Cullin/F-box protein class of E3 ubiquitin ligases and has been shown to direct degradation of pivotal cell-cycle regulatory proteins including cyclin D1 and the p53 antagonist MDM2. FBXO31 levels are normally low but increase substantially following genotoxic stress through a mechanism that remains to be determined...
January 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29343584/human-herpesvirus-8-interferon-regulatory-factors-1-and-3-mediate-replication-and-latency-activities-via-interactions-with-usp7-deubiquitinase
#15
Qiwang Xiang, Hyunwoo Ju, Qian Li, Szu-Chieh Mei, Daming Chen, Young Bong Choi, John Nicholas
Human herpesvirus 8 (HHV-8) encodes four viral interferon regulatory factors (vIRFs 1-4) that likely function to suppress innate immune and cellular stress responses through inhibitory interactions with various cellular proteins involved in these activities. It is notable that vIRFs 1 and 4 have been reported to interact with the deubiquitinase USP7, substrates of which include p53 and p53-targeting and destabilizing ubiquitin E3 ligase MDM2. Structural studies of vIRF-1 and vIRF-4 USP7-binding sequences in association with USP7 have been reported; both involve interactions with N-terminal domain residues of USP7, via EGPS and ASTS motifs in vIRF-1 and vIRF-4, respectively, but vIRF-4 residues also contact the catalytic site...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29339538/e6-protein-expressed-by-high-risk-hpv-activates-super-enhancers-of-the-egfr-and-c-met-oncogenes-by-destabilizing-the-histone-demethylase-kdm5c
#16
Xiaohua Chen, Jun Xian Loo, Xin Shi, Wenjun Xiong, Yong Guo, Haiqiang Ke, Mingkun Yang, Yanping Jiang, Siyu Xia, Min Zhao, Shan Zhong, ChunJiang He, Li Fu, Feng Li
The high-risk (HR) human papillomaviruses (HPV) are causative agents of anogenital tract dysplasia and cancers and a fraction of head and neck cancers. The HR HPV E6 oncoprotein possesses canonical oncogenic functions, such as p53 degradation and telomerase activation. It is also capable of stimulating expression of several oncogenes, but the molecular mechanism underlying these events are poorly understood. Here we provide evidence that HPV16 E6 physically interacts with histone H3K4 demethylase KDM5C, resulting in its degradation in an E3 ligase E6AP- and proteasome-dependent manner...
January 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/29339304/transformation-products-formation-of-ciprofloxacin-in-uva-led-and-uva-led-tio2-systems-impact-of-natural-organic-matter-characteristics
#17
Si Li, Jiangyong Hu
The role of natural organic matter (NOM) in contaminants removal by photolysis and photocatalysis has aroused increasing interest. However, evaluation of the influence of NOM characteristics on the transformation products (TPs) formation and transformation pathways of contaminants has rarely been performed. This study investigated the decomposition kinetics, mineralization, TPs formation and transformation pathways of antibiotic ciprofloxacin (CIP) during photolysis and photocatalysis in the presence of three commercial NOM isolates (Sigma-Aldrich humic acid (SAHA), Suwannee River humic acid (SRHA) and Suwannee River NOM (SRNOM)) by using UVA light emitting diode (UVA/LED) as an alternative light source...
January 9, 2018: Water Research
https://www.readbyqxmd.com/read/29337181/a-non-canonical-bcor-prc1-1-complex-represses-differentiation-programs-in-human-escs
#18
Zheng Wang, Micah D Gearhart, Yu-Wei Lee, Ishan Kumar, Bulat Ramazanov, Yan Zhang, Charles Hernandez, Alice Y Lu, Nils Neuenkirchen, Jingjing Deng, Jiaqi Jin, Yuval Kluger, Thomas A Neubert, Vivian J Bardwell, Natalia B Ivanova
Polycomb group proteins regulate self-renewal and differentiation in many stem cell systems. When assembled into two canonical complexes, PRC1 and PRC2, they sequentially deposit H3K27me3 and H2AK119ub histone marks and establish repressive chromatin, referred to as Polycomb domains. Non-canonical PRC1 complexes retain RING1/RNF2 E3-ubiquitin ligases but have unique sets of accessory subunits. How these non-canonical complexes recognize and regulate their gene targets remains poorly understood. Here, we show that the BCL6 co-repressor (BCOR), a member of the PRC1...
January 8, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29335415/usp48-restrains-resection-by-site-specific-cleavage-of-the-brca1-ubiquitin-mark-from-h2a
#19
Michael Uckelmann, Ruth M Densham, Roy Baas, Herrie H K Winterwerp, Alexander Fish, Titia K Sixma, Joanna R Morris
BRCA1-BARD1-catalyzed ubiquitination of histone H2A is an important regulator of the DNA damage response, priming chromatin for repair by homologous recombination. However, no specific deubiquitinating enzymes (DUBs) are known to antagonize this function. Here we identify ubiquitin specific protease-48 (USP48) as a H2A DUB, specific for the C-terminal BRCA1 ubiquitination site. Detailed biochemical analysis shows that an auxiliary ubiquitin, an additional ubiquitin that itself does not get cleaved, modulates USP48 activity, which has possible implications for its regulation in vivo...
January 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29333049/marine-derived-fungi-extracts-enhance-the-cytotoxic-activity-of-doxorubicin-in-nonsmall-cell-lung-cancer-cells-a459
#20
Bruno Castro-Carvalho, Alice A Ramos, Maria Prata-Sena, Fernanda Malhão, Márcia Moreira, Daniela Gargiulo, Tida Dethoup, Suradet Buttachon, Anake Kijjoa, Eduardo Rocha
Background: Drug resistance is a major concern in the current chemotherapeutic approaches and the combination with natural compounds may enhance the cytotoxic effects of the anticancer drugs. Therefore, this study evaluated the cytotoxicity of crude ethyl extracts of six marine-derived fungi - Neosartorya tsunodae KUFC 9213 (E1), Neosartorya laciniosa KUFC 7896 (E2), Neosartorya fischeri KUFC 6344 (E3), Aspergillus similanensis KUFA 0013 (E4), Neosartorya paulistensis KUFC 7894 (E5), and Talaromyces trachyspermum KUFC 0021 (E6) - when combined with doxorubicin (Dox), in seven human cancer cell lines...
December 2017: Pharmacognosy Research
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