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Ching-Hao Li, Chen-Wei Liu, Chi-Hao Tsai, Yi-Jen Peng, Yu-Hsuan Yang, Po-Lin Liao, Chen-Chen Lee, Yu-Wen Cheng, Jaw-Jou Kang
Aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, has been studied extensively in carcinogenesis through the genomic pathway. In recent years, AHR has also been reported to exert positive or negative effects on epithelial-mesenchymal transition (EMT), the crucial step in tumor malignant progression. However, the detailed mechanism remains controversial. Analysis of AHR-expression levels in non-small cell lung cancer cell lines and lung cancer tissues revealed an inverse correlation between AHR protein levels and tumor cell invasion and metastasis...
October 17, 2016: Archives of Toxicology
Sili Liu, Gabrielle L Boulianne
Neuralized Homology Repeats (NHRs) were first identified in Neuralized, an E3-ubiquitin ligase that plays a key role in the Notch signalling pathway. Since their original discovery, NHR domains have been shown to regulate protein-protein interactions in a broad range of developmental processes and in a wide variety of species from flies to humans. The NHR family of proteins can be categorized into three groups: (1) those that contain a RING finger, (2) those that contain a SOCS box and, (3) those that only have NHR domains...
October 14, 2016: Cellular Signalling
Kristen T Crowell, David I Soybel, Charles H Lang
Muscle deconditioning is commonly observed in patients surviving sepsis. Little is known regarding the molecular mechanisms regulating muscle protein homeostasis during the recovery or convalescence phase. We adapted a sepsis-recovery mouse model that uses cecal ligation and puncture (CLP), followed 24 h later by cecal resection and antibiotic treatment, to identify putative cellular pathways regulating protein synthesis and breakdown in skeletal muscle. Ten days after CLP, body weight and food consumption did not differ between control and sepsis-recovery mice, but gastrocnemius weight was reduced...
October 5, 2016: Shock
Fumiaki Ohtake, Yasushi Saeki, Satoshi Ishido, Jun Kanno, Keiji Tanaka
Polyubiquitin chains of different topologies regulate diverse cellular processes. K48- and K63-linked chains, the two most abundant chain types, regulate proteolytic and signaling pathways, respectively. Although recent studies reported important roles for heterogeneous chains, the functions of branched ubiquitin chains remain unclear. Here, we show that the ubiquitin chain branched at K48 and K63 regulates nuclear factor κB (NF-κB) signaling. A mass-spectrometry-based quantification strategy revealed that K48-K63 branched ubiquitin linkages are abundant in cells...
October 8, 2016: Molecular Cell
Fei Lu, Xiaojun Wu, Feng Yin, Christina Chia-Fang Lee, Min Yu, Ivailo S Mihaylov, Jiekai Yu, Hong Sun, Hui Zhang
DNA replication licensing occurs on chromatin, but how the chromatin template is regulated for replication remains mostly unclear. Here, we have analyzed the requirement of histone methyltransferases for a specific type of replication: the DNA re-replication induced by the downregulation of either Geminin, an inhibitor of replication licensing protein CDT1, or the CRL4CDT2 ubiquitin E3 ligase. We found that siRNA-mediated reduction of essential components of the MLL-WDR5-RBBP5 methyltransferase complexes including WDR5 or RBBP5, which transfer methyl groups to histone H3 at K4 (H3K4), suppressed DNA re-replication and chromosomal polyploidy...
October 15, 2016: Biology Open
Shengyuan Zeng, Yangyang Wang, Ting Zhang, Lu Bai, Yalan Wang, Changzhu Duan
UHRF2 is a ubiquitin-protein ligase E3 that regulates cell cycle, genomic stability and epigenetics. We conducted a co-immunoprecipitation assay and found that TIP60 and HDAC1 interact with UHRF2. We previously demonstrated that UHRF2 regulated H3K9ac and H3K14ac differentially in normal and cancer cells. However, the accurate signal transduction mechanisms were not clear. In this study, we found that TIP60 acted downstream of UHRF2 to regulate H3K9ac and H3K14ac expression. TIP60 is stabilized in normal cells by UHRF2 ubiquitination...
October 14, 2016: Protein & Cell
Kristi J Warren, Xi Fang, Nagaraj M Gowda, Joshua J Thompson, Nicola M Heller
Lung M2 macrophages are regulators of airway inflammation, associated with poor lung function in allergic asthma. Previously, we demonstrated that IL-4-induced M2 gene expression correlated with tyrosine phosphorylation of the insulin receptor substrate (IRS)-2 in macrophages. We hypothesized that negative regulation of IRS-2 activity following IL-4 stimulation is dependent upon serine phosphorylation of IRS-2. Herein, we describe an inverse relationship between tyrosine phosphorylation (pY) and serine phosphorylation (pS) of IRS-2 following IL-4 stimulation...
October 14, 2016: Journal of Biological Chemistry
Dirk Landgraf, Dann Huh, Erinc Hallacli, Susan Lindquist
Gene tagging with fluorescent proteins is commonly applied to investigate the localization and dynamics of proteins in their cellular environment. Ideally, a fluorescent tag is genetically inserted at the endogenous locus at the N- or C- terminus of the gene of interest without disrupting regulatory sequences including the 5' and 3' untranslated region (UTR) and without introducing any extraneous unwanted "scar" sequences, which may create unpredictable transcriptional or translational effects. We present a reliable, low-cost, and highly efficient method for the construction of such scarless C-terminal and N-terminal fusions with fluorescent proteins in yeast...
2016: PloS One
Young Bong Choi, Noula Shembade, Kislay Parvatiyar, Siddharth Balachandran, Edward William Harhaj
The host response to RNA virus infection consists of an intrinsic innate immune response and the induction of apoptosis as mechanisms to restrict viral replication. The mitochondrial adaptor molecule MAVS plays critical roles in coordinating both virus-induced type I interferon production and apoptosis; however, the regulation of MAVS-mediated apoptosis is poorly understood. Here, we show that the adaptor protein TAX1BP1 functions as a negative regulator of virus-induced apoptosis. TAX1BP1-deficient cells are highly sensitive to apoptosis in response to infection with the RNA viruses vesicular stomatitis virus and Sendai virus and transfection with poly(I:C)...
October 10, 2016: Molecular and Cellular Biology
Matthew Cushing, Jonathan Hooshmand, Bryan Pomares, Gillian Hotz
Inspired by Swedish legislation, Vision Zero policies are being adopted in the United States with increasing frequency. Although some view the goal of eliminating serious injury and death on the road system as impractical, Sweden's lower rates of road-related injury and death provide compelling evidence that more can be done to improve US cycling safety. We examine existing Vision Zero and cycling-related literature to highlight the central components of the Swedish policy, with the goal of providing evidence-based recommendations for successful implementation of similar policies in the United States...
October 13, 2016: American Journal of Public Health
Timothy F Leslie, Erica J Street, Paul L Delamater, Y Tony Yang, Kathryn H Jacobsen
OBJECTIVES: To compile substate-level data on US school-age children's vaccination rates. METHODS: For states that did not have suitable data online, in 2015 we submitted information requests to the state health department and followed up with the state's Freedom of Information Act when necessary. RESULTS: The accessibility, scale, and types of vaccination data varied considerably. Whereas 26 states provided data online, 14 released data only after a Freedom of Information Act request...
October 13, 2016: American Journal of Public Health
Brittany M Charlton, Heather L Corliss, Donna Spiegelman, Kerry Williams, S Bryn Austin
OBJECTIVES: To compare changes in self-reported sexual orientation of women living in states with any recognition of same-sex relationships (e.g., hospital visitation, domestic partnerships) with those of women living in states without such recognition. METHODS: We calculated the likelihood of women in the Nurses' Health Study II (n = 69 790) changing their reported sexual orientation between 1995 and 2009. RESULTS: We used data from the Nurses' Health Study II and found that living in a state with same-sex relationship recognition was associated with changing one's reported sexual orientation, particularly from heterosexual to sexual minority...
October 13, 2016: American Journal of Public Health
Bernadet Garcia-Silva, Eric Handler, Julia Wolfe
Food insecurity is a global issue that arises owing to systemic socioeconomic inequities and environmental constraints. To highlight the existence and the extent of food insecurity and food waste, the Orange County Health Department in Orange County, California, created a coalition called "Waste Not Orange County." Orange County is the sixth most populous county in California and has the highest median income, yet 11.4% of those residing in Orange County are food insecure, and 24.0% live in poverty. The overall vision of the coalition is to mitigate hunger in Orange County by educating the community about food donations, identifying food-insecure individuals, and connecting those individuals to sources of food...
October 13, 2016: American Journal of Public Health
Pooja K Mehta, Marcus A Bachhuber, Roy Hoffman, Sindhu K Srinivas
OBJECTIVES: To understand the effect of unintentional injuries (e.g., drug overdose), suicide, and homicide on pregnancy-associated death (death during or within 1 year of pregnancy). METHODS: We analyzed all cases of pregnancy-associated death among Philadelphia, Pennsylvania, residents from 2010 to 2014, examining cause of death, contributing factors, and history of health care use. RESULTS: Approximately half (49%; 42 of 85) of pregnancy-associated deaths were from unintentional injuries (n = 31), homicide (n = 8), or suicide (n = 3); drug overdose was the leading cause (n = 18)...
October 13, 2016: American Journal of Public Health
Zhongwei Wang, Yali Wang, Hongtao Ren, Yingying Jin, Ya Guo
Zinc and ring finger 3 (ZNRF3), which belongs to the E3 ubiquitin ligase family is involved in the progression and development of cancer. However, the expression and function of ZNRF3 in human nasopharyngeal carcinoma (NPC) remains unclear. Thus, the aim of this paper was to investigate the role of ZNRF3 in human nasopharyngeal carcinoma. Our results showed that ZNRF3 was downregulated in nasopharyngeal carcinoma cell lines. Restoration of ZNRF3 significantly inhibited the proliferation of NPC cells and tumor xenograft growth in vivo...
October 11, 2016: Oncology Research
Lu Yu, Jun Li, Sanpeng Xu, Mariajose Navia Miranda, Guoping Wang, Yaqi Duan
BACKGROUND: Xp11.2 translocation/transcription factor E3 (TFE3) rearrangement renal cell carcinoma (RCC) is a rare subtype of RCC with limited clinical and pathological data. CASE PRESENTATION: Here we present an unusual high-grade Xp11.2 translocation RCC with a rhabdoid feature and SMARCB1 (INI1) inactivation in a 40-year-old man with end-stage kidney disease. The histological examination of the dissected left renal tumor showed an organoid architecture of the eosinophilic or clear neoplastic cells with necrosis and high mitotic activity...
October 12, 2016: Diagnostic Pathology
Yuya Yamagishi, Marc Tessier-Lavigne
Axon degeneration is a tightly regulated, self-destructive program that is a critical feature of many neurodegenerative diseases, but the molecular mechanisms regulating this program remain poorly understood. Here, we identify S-phase kinase-associated protein 1A (Skp1a), a core component of a Skp/Cullin/F-box (SCF)-type E3 ubiquitin ligase complex, as a critical regulator of axon degeneration after injury in mammalian neurons. Depletion of Skp1a prolongs survival of injured axons in vitro and in the optic nerve in vivo...
October 11, 2016: Cell Reports
Bo Wu, Bomin Guo, Jie Kang, Xianzhao Deng, Youben Fan, Xiaoping Zhang, Kaixing Ai
Smad ubiquitin regulatory factor 2 (Smurf2) is an E3 ubiquitin ligase that regulates transforming growth factor β (TGF-β)/Smad signaling and is implicated in a wide range of cellular responses. However, the exact mechanism whereby Smurf2 controls TGF-β-induced signaling pathways remains unknown. Here, we identified the relationship between the alternate TGF-β signaling pathways: TGF-β/PI3K/Akt/β-catenin and TGF-β/Smad2/3/FoxO1/PUMA and Smurf2. The results showed that TGF-β promoted proliferation, invasion, and migration of human pancreatic carcinoma (PANC-1) cells through the PI3K/Akt/β-catenin pathway...
October 11, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Wenfeng Wang, Anne Wairimu Ndungu, Jun Wang
Occurrence and distribution of eight selected endocrine-disrupting compounds (EDCs), including estrone (E1), 17α-ethinylestradiol (EE2), 17α-estradiol (αE2), 17β-estradiol (βE2), estriol (E3), bisphenol A (BPA), 4-nonylphenol (NP), and 4-octylphenol (OP), were investigated in surface water and sediments of the Three Gorges Reservoir region (TGRR). The mean concentrations of E1, αE2, βE2, E3, EE2, BPA, NP, and OP were 10.3, 3.3, 3.7, 17.2, 7.8, 26.6, 10.8, and 32.3 ng L(-1) respectively in surface water and 2...
October 11, 2016: Archives of Environmental Contamination and Toxicology
Arno F Alpi, Viduth Chaugule, Helen Walden
Ubiquitin signalling is a fundamental eukaryotic regulatory system, controlling diverse cellular functions. A cascade of E1, E2, and E3 enzymes is required for assembly of distinct signals, whereas an array of deubiquitinases and ubiquitin-binding modules edit, remove, and translate the signals. In the centre of this cascade sits the E2-conjugating enzyme, relaying activated ubiquitin from the E1 activating enzyme to the substrate, usually via an E3 ubiquitin ligase. Many disease states are associated with dysfunction of ubiquitin signalling, with the E3s being a particular focus...
October 15, 2016: Biochemical Journal
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