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https://www.readbyqxmd.com/read/29693039/demethylase-jmjd6-as-a-new-regulator-of-interferon-signaling-effects-of-hcv-and-ethanol-metabolism
#1
Murali Ganesan, Irina Tikhanovich, Shiva Shankar Vangimalla, Raghubendra Singh Dagur, Weimin Wang, Larisa I Poluektova, Yimin Sun, David F Mercer, Dean Tuma, Steven A Weinman, Kusum K Kharbanda, Natalia A Osna
Background & Aims: Alcohol-induced progression of hepatitis C virus (HCV) infection is related to dysfunction of innate immunity in hepatocytes. Endogenously produced interferon (IFN)α induces activation of interferon-stimulated genes (ISGs) via triggering of the Janus kinase-signal transducer and activator of transcription 1 (STAT1) pathway. This activation requires protein methyltransferase 1-regulated arginine methylation of STAT1. Here, we aimed to study whether STAT1 methylation also depended on the levels of demethylase jumonji domain-containing 6 protein (JMJD6) and whether ethanol and HCV affect JMJD6 expression in hepatocytes...
2018: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29628309/jmjd6-licenses-er%C3%AE-dependent-enhancer-and-coding-gene-activation-by-modulating-the-recruitment-of-the-carm1-med12-co-activator-complex
#2
Wei-Wei Gao, Rong-Quan Xiao, Wen-Juan Zhang, Yi-Ren Hu, Bing-Ling Peng, Wen-Juan Li, Yao-Hui He, Hai-Feng Shen, Jian-Cheng Ding, Qi-Xuan Huang, Tian-Yi Ye, Ying Li, Zhi-Ying Liu, Rong Ding, Michael G Rosenfeld, Wen Liu
Whereas the actions of enhancers in gene transcriptional regulation are well established, roles of JmjC-domain-containing proteins in mediating enhancer activation remain poorly understood. Here, we report that recruitment of the JmjC-domain-containing protein 6 (JMJD6) to estrogen receptor alpha (ERα)-bound active enhancers is required for RNA polymerase II recruitment and enhancer RNA production on enhancers, resulting in transcriptional pause release of cognate estrogen target genes. JMJD6 is found to interact with MED12 in the mediator complex to regulate its recruitment...
April 4, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29620141/jmjd6-exerts-function-in-neuropathic-pain-by-regulating-nf%C3%A2-%C3%AE%C2%BAb-following-peripheral-nerve-injury-in-rats
#3
Cen Wen, Mengyuan Xu, Cheng Mo, Zhigang Cheng, Qulian Guo, Xiaoyan Zhu
Treatment of neuropathic pain (NPP) continues to be a major challenge, and the underlying mechanisms remain to be elucidated. Previous studies have demonstrated that histone methylation is important in synaptic plasticity of the nervous system and may affect nuclear factor‑κB (NF‑κB) signaling through epigenetic mechanisms. The present study aimed to investigate the role of Jumonji C domain 6 (JMJD6), a histone demethylase, in a chronic constriction injury (CCI) model of NPP. On the third day post‑CCI surgery, a JMJD6 overexpressing lentiviral vector (LV‑JMJD6) was intrathecally injected in the rats...
April 3, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29605300/lncrna-malat1-promotes-cpc-proliferation-and-migration-in-hypoxia-by-up-regulation-of-jmjd6-via-sponging-mir-125
#4
Linlin Li, Qiuyun Wang, Zhize Yuan, Anqing Chen, Zuyun Liu, Zhe Wang, Haiqing Li
The death of cardiomyocytes after myocardial infarction (MI) often leads to ventricular remodeling as well as heart failure (HF). The cardiac progenitor cells (CPCs) have the ability to regenerate functional heart muscle in patients after MI, which provides a promising method for MI-induced HF therapy. However, to date, CPCs can easily lose their proliferation ability in the infarcted myocardium. Therefore, exploring the mechanism for CPC proliferation is essential for CPC-based therapy in MI-induced HF. A previous study indicated that a hypoxic environment is essential for CPC proliferation, but the mechanism is not yet clear...
March 29, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29373688/compromised-jmjd6-histone-demethylase-activity-impacts-on-vhl-gene-repression-in-preeclampsia
#5
Sruthi Alahari, Martin Post, Alessandro Rolfo, Rosanna Weksberg, Isabella Caniggia
Context: The von Hippel Lindau (VHL) protein is a key executor of the cellular hypoxic response that is compromised in preeclampsia, a serious disorder complicating 5-7% of pregnancies. To date, the mechanisms controlling VHL gene expression in the human placenta remain elusive. Objective: We examined VHL epigenetic regulation in normal pregnancy and in preeclampsia, a pathology characterized by placental hypoxia. Design, Setting, and Participants: Placentae were obtained from early-onset (E-PE: n=56; <34 weeks of gestation) and late onset preeclampsia (L-PE: n=19; ≥ 34 weeks of gestation)...
January 24, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29338076/hypoxia-inducible-transcription-factors-hif1a-and-hif2a-increase-in-aging-mucosal-tissues
#6
Jeffrey L Ebersole, Michael John Novak, Luis Orraca, Janis Martinez-Gonzalez, Sreenatha Kirakodu, Kuey C Chen, Arnold Stromberg, Octavio A Gonzalez
Hypoxia (i.e. oxygen deprivation) activates the hypoxia-signalling pathway, primarily via hypoxia-inducible transcription factors (HIF) for numerous target genes, which mediate angiogenesis, metabolism and coagulation, among other processes to try to replenish tissues with blood and oxygen. Hypoxia signalling dysregulation also commonly occurs during chronic inflammation. We sampled gingival tissues from rhesus monkeys (Macaca mulatta; 3-25 years old) and total RNA was isolated for microarray analysis. HIF1A, HIF1B and HIF2A were significantly different in healthy aged tissues, and both HIF1A and HIF3A were positively correlated with aging...
January 16, 2018: Immunology
https://www.readbyqxmd.com/read/29229759/jmjd6-induces-hotair-an-oncogenic-lincrna-by-physically-interacting-with-its-proximal-promoter
#7
Antara Biswas, Abhijith Shettar, Geetashree Mukherjee, Paturu Kondaiah, Kartiki V Desai
Using microarray analysis, we found that HOX transcript antisense intergenic RNA (HOTAIR) is up-regulated by Jumonji domain containing-6 (JMJD6), a bifunctional lysyl hydroxylase and arginine demethylase. In breast cancer, both JMJD6 and HOTAIR RNAs increase tumor growth and associate with poor prognosis but no molecular relationship between them is known. We show that overexpression of JMJD6 increased HOTAIR expression and JMJD6 siRNAs suppressed it in ER+ MCF-7, triple negative MDA-MB-231 and non-breast cancer HEK 293 cells...
January 15, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29187213/jmjd6-promotes-melanoma-carcinogenesis-through-regulation-of-the-alternative-splicing-of-pak1-a-key-mapk-signaling-component
#8
Xujun Liu, Wenzhe Si, Xinhua Liu, Lin He, Jie Ren, Ziran Yang, Jianguo Yang, Wanjin Li, Shumeng Liu, Fei Pei, Xiaohan Yang, Luyang Sun
BACKGROUND: Melanoma, originated from melanocytes located on the basal membrane of the epithelial tissue, is the most aggressive form of skin cancer that accounts for 75% of skin cancer-related death. Although it is believed that BRAF mutation and the mitogen-activated protein kinase (MAPK) pathway play critical roles in the pathogenesis of melanoma, how the MAPK signaling is regulated in melanoma carcinogenesis is still not fully understood. METHODS: We characterized JMJD6 expression in melanoma tissue array by immunohistochemistry analysis...
November 29, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/29176719/structural-mechanism-of-the-oxygenase-jmjd6-recognition-by-the-extraterminal-et-domain-of-brd4
#9
Tsuyoshi Konuma, Di Yu, Chengcheng Zhao, Ying Ju, Rajal Sharma, Chunyan Ren, Qiang Zhang, Ming-Ming Zhou, Lei Zeng
Jumonji domain-containing protein 6 (JMJD6) is a member of the Jumonji C family of Fe(II) and 2-oxoglutarate (2OG) dependent oxygenases. It possesses unique bi-functional oxygenase activities, acting as both an arginine demethylase and a lysyl-hydroxylase. JMJD6 has been reported to be over-expressed in oral, breast, lung, and colon cancers and plays important roles in regulation of transcription through interactions with transcription regulator BRD4, histones, U2AF65, Luc7L3, and SRSF11. Here, we report a structural mechanism revealed by NMR of JMJD6 recognition by the extraterminal (ET) domain of BRD4 in that a JMJD6 peptide (Lys84-Asn96) adapts an α-helix when bound to the ET domain...
November 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29023917/protein-arginine-methyl-transferase-1-and-jumonji-c-domain-containing-protein-6-dependent-arginine-methylation-regulate-hepatocyte-nuclear-factor-4-alpha-expression-and-hepatocyte-proliferation-in-mice
#10
Jie Zhao, Abby Adams, Ben Roberts, Maura O'Neil, Anusha Vittal, Timothy Schmitt, Sean Kumer, Josiah Cox, Zhuan Li, Steven A Weinman, Irina Tikhanovich
Alcohol is a well-established risk factor for hepatocellular carcinoma (HCC), but the mechanisms by which it promotes liver cancer are not well understood. Several studies have shown that cellular protein arginine methylation is inhibited by alcohol. Arginine methylation is controlled by the reciprocal activity of protein arginine methyltransferases, primarily protein arginine methyl transferase 1 (PRMT1), and a demethylase Jumonji C domain-containing protein 6 (JMJD6). The aim of this study was to explore the role of arginine methylation changes in alcohol pathogenesis...
March 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28972166/histone-arginine-demethylase-jmjd6-is-linked-to-stress-granule-assembly-through-demethylation-of-the-stress-granule-nucleating-protein-g3bp1
#11
Wei-Chih Tsai, Lucas C Reineke, Antrix Jain, Sung Yun Jung, Richard E Lloyd
Stress granules (SG) are membrane-less organelles that are condensates of stalled translation initiation complexes and mRNAs. SG formation is a cytoprotective response to environmental stress and results from protein interactions involving regions of low amino acid complexity and poorly defined post-translational modifications of SG components. Many RNA-binding proteins are methylated, and we previously demonstrated that the potent SG-nucleating protein G3BP1 is methylated by protein arginine methyltransferase 1 and 5 (PRMT1 and PRMT5)...
November 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28882645/mir-770-inhibits-tumorigenesis-and-emt-by-targeting-jmjd6-and-regulating-wnt-%C3%AE-catenin-pathway-in-non-small-cell-lung-cancer
#12
Zhiwei Zhang, Yang Yang, Xiuqiang Zhang
AIMS: MicroRNAs (miRNAs) plays important role in development and disease, especially in cancer including non-small cell lung cancer (NSCLC). However, the role of miR-770 in NSCLC remains unclear. In this study, we aimed to study the function and mechanism of miR-770 in tumorigenesis of NSCLC. MAIN METHODS: RT-qPCR was used to measure the expression levels of miR-770 in NSCLC tissues and cells. MTT assay, colony formation assay, flow cytometric analysis and transwell migration and invasion assays were performed to investigate the role of miR-770 in NSCLC cells...
November 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/28793959/corrigendum-to-thymic-epithelial-cell-specific-deletion-of-jmjd6-reduces-aire-protein-expression-and-exacerbates-disease-development-in-a-mouse-model-of-autoimmune-diabetes-biochemical-and-biophysical-research-communications-489-1-2017-8-13
#13
Toyoshi Yanagihara, Takahiro Tomino, Takehito Uruno, Yoshinori Fukui
No abstract text is available yet for this article.
September 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28790175/antibody-mediated-blockade-of-jmjd6-interaction-with-collagen-i-exerts-antifibrotic-and-antimetastatic-activities
#14
Silvia Miotti, Alessandro Gulino, Renata Ferri, Mariella Parenza, Agnieszka Chronowska, Daniele Lecis, Sabina Sangaletti, Elda Tagliabue, Claudio Tripodo, Mario P Colombo
JMJD6 is known to localize in the nucleus, exerting histone arginine demethylase and lysyl hydroxylase activities. A novel localization of JMJD6 in the extracellular matrix, resulting from its secretion as a soluble protein, was unveiled by a new anti-JMJD6 mAb called P4E11, which was developed to identify new targets in the stroma. Recombinant JMJD6 binds with collagen type I (Coll-I), and distinct JMJD6 peptides interfere with collagen fibrillogenesis, collagen-fibronectin interaction, and adhesion of human tumor cells to the collagen substrate...
December 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28710103/transcription-elongation-factors-are-potential-targets-in-glioblastoma
#15
(no author information available yet)
JMJD6 promotes transcription pause-release and elongation and glioblastoma cell survival in vivo.
July 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28678782/transcription-elongation-factors-represent-in-vivo-cancer-dependencies-in-glioblastoma
#16
Tyler E Miller, Brian B Liau, Lisa C Wallace, Andrew R Morton, Qi Xie, Deobrat Dixit, Daniel C Factor, Leo J Y Kim, James J Morrow, Qiulian Wu, Stephen C Mack, Christopher G Hubert, Shawn M Gillespie, William A Flavahan, Thomas Hoffmann, Rohit Thummalapalli, Michael T Hemann, Patrick J Paddison, Craig M Horbinski, Johannes Zuber, Peter C Scacheri, Bradley E Bernstein, Paul J Tesar, Jeremy N Rich
Glioblastoma is a universally lethal cancer with a median survival time of approximately 15 months. Despite substantial efforts to define druggable targets, there are no therapeutic options that notably extend the lifespan of patients with glioblastoma. While previous work has largely focused on in vitro cellular models, here we demonstrate a more physiologically relevant approach to target discovery in glioblastoma. We adapted pooled RNA interference (RNAi) screening technology for use in orthotopic patient-derived xenograft models, creating a high-throughput negative-selection screening platform in a functional in vivo tumour microenvironment...
July 20, 2017: Nature
https://www.readbyqxmd.com/read/28592121/inhibition-of-jmjd6-expression-reduces-the-proliferation-migration-and-invasion-of-neuroglioma-stem-cells
#17
D X Zhou, D Zhou, S Q Zhan, P Wang, K Qin, W Gan, X F Lin
Neuroglioma is the most common form of human primary malignant brain tumor, more and more studies recently showed only a small subpopulation of glioma cells which called glioma stem cells have true tumorigenic potential. Meanwhile, it was reported the overexpression of JMJD6 protein is closely involvement with the occurrence and development of multiple tumors, and JMJD6 is required for the differentiation of multiple organ, tissues and cells during embryogenesis. However, the influence of JMJD6 overexpression on neuroglioma development is unclear now...
June 8, 2017: Neoplasma
https://www.readbyqxmd.com/read/28587176/bifunctional-enzyme-jmjd6-contributes-to-multiple-disease-pathogenesis-new-twist-on-the-old-story
#18
REVIEW
Shiva Shankar Vangimalla, Murali Ganesan, Kusum K Kharbanda, Natalia A Osna
Jumonji domain-containing protein 6 (JMJD6) is a non-heme Fe(II) 2-oxoglutarate (2OG)-dependent oxygenase with arginine demethylase and lysyl hydroxylase activities. Its initial discovery as a dispensable phosphatidylserine receptor (PSR) in the cell membrane of macrophages for phagocytosis was squashed by newer studies which revealed its nuclear localization and bifunctional enzymatic activity. Though its interaction with several nuclear and cytoplasmic target proteins has been demonstrated, the exact mechanisms and clinical significance of these various biologic interplays are not yet well established...
June 1, 2017: Biomolecules
https://www.readbyqxmd.com/read/28546003/thymic-epithelial-cell-specific-deletion-of-jmjd6-reduces-aire-protein-expression-and-exacerbates-disease-development-in-a-mouse-model-of-autoimmune-diabetes
#19
Toyoshi Yanagihara, Takahiro Tomino, Takehito Uruno, Yoshinori Fukui
Thymic epithelial cells (TECs) establish spatially distinct microenvironments in which developing T cells are selected to mature or die. A unique property of medullary TECs is their expression of thousands of tissue-restricted self-antigens that is largely under the control of the transcriptional regulator Aire. We previously showed that Jmjd6, a lysyl hydroxylase for splicing regulatory proteins, is important for Aire protein expression and that transplantation of Jmjd6-deficient thymic stroma into athymic nude mice resulted in multiorgan autoimmunity...
July 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28364140/insights-into-jumonji-c-domain-containing-protein-6-jmjd6-a-multifactorial-role-in-foot-and-mouth-disease-virus-replication-in-cells
#20
REVIEW
Paul Lawrence, Elizabeth Rieder
The Jumonji C-domain containing protein 6 (JMJD6) has had a convoluted history, and recent reports indicating a multifactorial role in foot-and-mouth disease virus (FMDV) infection have further complicated the functionality of this protein. It was first identified as the phosphatidylserine receptor on the cell surface responsible for recognizing phosphatidylserine on the surface of apoptotic cells resulting in their engulfment by phagocytic cells. Subsequent study revealed a nuclear subcellular localization, where JMJD6 participated in lysine hydroxylation and arginine demethylation of histone proteins and other non-histone proteins...
June 2017: Virus Genes
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