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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
Janice Kwok, Marie O'Shea, David A Hume, Andreas Lengeling
Lysyl hydroxylation and arginyl demethylation are post-translational events that are important for many cellular processes. The jumonji domain containing protein 6 (JMJD6) has been reported to catalyze both lysyl hydroxylation and arginyl demethylation on diverse protein substrates. It also interacts directly with RNA. This review summarizes knowledge of JMJD6 functions that have emerged in the last 15 years and considers how a single Jumonji C (JmjC) domain-containing enzyme can target so many different substrates...
2017: Frontiers in Genetics
Yi Fang Lee, Lance David Miller, Xiu Bin Chan, Michael A Black, Brendan Pang, Chee Wee Ong, Manuel Salto-Tellez, Edison T Liu, Kartiki V Desai
No abstract text is available yet for this article.
March 28, 2017: Breast Cancer Research: BCR
Jia Yi, Hai-Feng Shen, Jin-Song Qiu, Ming-Feng Huang, Wen-Juan Zhang, Jian-Cheng Ding, Xiao-Yan Zhu, Yu Zhou, Xiang-Dong Fu, Wen Liu
JMJD6, a jumonji C (Jmj C) domain-containing protein demethylase and hydroxylase, has been implicated in an array of biological processes. It has been shown that JMJD6 interacts with and hydroxylates multiple serine/arginine-rich (SR) proteins and SR related proteins, including U2AF65, all of which are known to function in alternative splicing regulation. However, whether JMJD6 is widely involved in alternative splicing and the molecular mechanism underlying JMJD6-regulated alternative splicing have remained incompletely understood...
April 7, 2017: Nucleic Acids Research
Junhu Wan, Weizhi Xu, Jun Zhan, Ji Ma, Xueying Li, Yuping Xie, Jiadong Wang, Wei-Guo Zhu, Jianyuan Luo, Hongquan Zhang
HOXB9 is a homeobox domain-containing transcription factor, playing an important role in embryonic development and cancer progression. However, the precise post-translational modifications (PTMs) of HOXB9 and the corresponding roles are unclear. Here, we report that acetyltransferase p300/CBP-associated factor (PCAF) interacts with and acetylates HOXB9 both in vivo and in vitro Conversely, the acetylation of HOXB9 can be reversed by deacetylase SIRT1. Furthermore, we found that HOXB9 is acetylated at lysine 27 (AcK27)...
December 15, 2016: Nucleic Acids Research
Coralie Poulard, Laura Corbo, Muriel Le Romancer
Protein arginine methylation is a common post-translational modification involved in numerous cellular processes including transcription, DNA repair, mRNA splicing and signal transduction. Currently, there are nine known members of the protein arginine methyltransferase (PRMT) family, but only one arginine demethylase has been identified, namely the Jumonji domain-containing 6 (JMJD6). Although its demethylase activity was initially challenged, its dual activity as an arginine demethylase and a lysine hydroxylase is now recognized...
October 11, 2016: Oncotarget
Ping Yu, Lexiang Ji, Kevin J Lee, Miao Yu, Chuan He, Suresh Ambati, Elizabeth C McKinney, Crystal Jackson, Clifton A Baile, Robert J Schmitz, Richard B Meagher
The reprogramming of cellular memory in specific cell types, and in visceral adipocytes in particular, appears to be a fundamental aspect of obesity and its related negative health outcomes. We explored the hypothesis that adipose tissue contains epigenetically distinct subpopulations of adipocytes that are differentially potentiated to record cellular memories of their environment. Adipocytes are large, fragile, and technically difficult to efficiently isolate and fractionate. We developed fluorescence nuclear cytometry (FNC) and fluorescence activated nuclear sorting (FANS) of cellular nuclei from visceral adipose tissue (VAT) using the levels of the pan-adipocyte protein, peroxisome proliferator-activated receptor gamma-2 (PPARg2), to distinguish classes of PPARg2-Positive (PPARg2-Pos) adipocyte nuclei from PPARg2-Negative (PPARg2-Neg) leukocyte and endothelial cell nuclei...
2016: PloS One
Olga Aprelikova, Kenny Chen, Lara H El Touny, Constance Brignatz-Guittard, Justin Han, Tinghu Qiu, Howard H Yang, Maxwell P Lee, Min Zhu, Jeffrey E Green
BACKGROUND: Oncogene overexpression in primary cells often triggers the induction of a cellular safeguard response promoting senescence or apoptosis. Secondary cooperating genetic events are generally required for oncogene-induced tumorigenesis to overcome these biologic obstacles. We employed comparative genomic hybridization for eight genetically engineered mouse models of mammary cancer to identify loci that might harbor genes that enhance oncogene-induced tumorigenesis. RESULTS: Unlike many other mammary tumor models, the MMTV-Myc tumors displayed few copy number variants except for amplification of distal mouse chromosome 11 in 80 % of the tumors (syntenic to human 17q23-qter often amplified in human breast cancer)...
2016: Clinical Epigenetics
Yu-Jie Hu, Anthony N Imbalzano
Emerging evidence suggests Jumonji domain-containing proteins are epigenetic regulators in diverse biological processes including cellular differentiation and proliferation. RNA interference-based analyses combined with gene expression profiling can effectively characterize the cellular functions of these enzymes. We found that the depletion of Jumonji domain-containing protein 6 (JMJD6) and its paralog protein Jumonji domain-containing protein 4 (JMJD4) individually by small hairpin RNAs (shRNAs) slowed cell proliferation of mouse NIH3T3 fibroblasts...
2016: Scientific Data
Paul Lawrence, Juan Pacheco, Carolina Stenfeldt, Jonathan Arzt, Devendra K Rai, Elizabeth Rieder
A companion study reported Jumonji-C domain containing protein 6 (JMJD6) is involved in an integrin- and HS-independent pathway of FMDV infection in CHO cells. JMJD6 localization was investigated in animal tissues from cattle infected with either wild type A24-FMDV (A24-WT) or mutant FMDV (JMJD6-FMDV) carrying E95K/S96L and RGD to KGE mutations in VP1. Additionally, pathogenesis of mutant JMJD6-FMDV was investigated in cattle through aerosol and intraepithelial lingual (IEL) inoculation. Interestingly, JMJD6-FMDV pathogenesis was equivalent to A24-WT administered by IEL route...
May 2016: Virology
Paul Lawrence, Devendra Rai, Joseph S Conderino, Sabena Uddowla, Elizabeth Rieder
Foot-and-mouth disease virus (FMDV) utilizes four integrins (αvβ1, αvβ3, αvβ6, and αvβ8) as its primary cell receptor. During cell culture propagation, FMDV frequently adapts to use heparan sulfate (HS), and rarely utilizes an unidentified third receptor. Capsid mutations acquired by a soluble integrin resistant FMDV cause (i) adaptation to CHO-677 cells (ii) increased affinity to membrane-bound Jumonji C-domain containing protein 6 (JMJD6) (iii) induced JMJD6 re-localization from the cell surface and cytoplasm to the nucleus...
May 2016: Virology
Kirsten R Palmer, Stephen Tong, Laura Tuohey, Ping Cannon, Louie Ye, Natalie J Hannan, Fiona C Brownfoot, Sebastián E Illanes, Tu'uhevaha J Kaitu'u-Lino
The anti-angiogenic protein, soluble fms-like tyrosine kinase-1 (sFLT-1), plays a central role in preeclamptic pathophysiology. A splice variant of FLT-1 (VEGF receptor 1), sFLT-1 is released in excessive amounts from the preeclamptic placenta into the maternal circulation, where it causes endothelial dysfunction manifesting as end-organ disease. However, the mechanisms regulating its production within the placenta remain poorly understood. Recently it was shown in endothelial cells that Jumonji domain containing protein 6 (JMJD6) hydroxylates U2 small nuclear ribonucleoprotein auxiliary factor 65-kDa subunit (U2AF65, a component of the splicesome)...
March 2016: Biology of Reproduction
Chang-Ryul Lee, Sung Hee Lee, Nicole Kristina Rigas, Reuben H Kim, Mo K Kang, No-Hee Park, Ki-Hyuk Shin
Cancer stem cells (CSCs) are defined as a small subpopulation of cancer cells within a tumor and responsible for initiation and maintenance of tumor growth. Thus, understanding of molecular regulators of CSCs is of paramount importance for the development of effective cancer therapies. Here, we identified jumonji domain-containing protein 6 (JMJD6) as a novel molecular regulator of oral CSCs. JMJD6 is highly expressed in CSC-enriched populations of human oral squamous cell carcinoma (OSCC) cell lines. Moreover, immunohistochemical staining revealed significantly high level of JMJD6 in OSCC tissues compared to normal human oral epithelia, suggesting that expression of JMJD6 positively correlates with oral carcinogenesis...
February 2016: Carcinogenesis
Toyoshi Yanagihara, Fumiyuki Sanematsu, Tetsuya Sato, Takehito Uruno, Xuefeng Duan, Takahiro Tomino, Yosuke Harada, Mayuki Watanabe, Yuqing Wang, Yoshihiko Tanaka, Yoichi Nakanishi, Mikita Suyama, Fukui Yoshinori
The thymus has spatially distinct microenvironments, the cortex and the medulla, where the developing T-cells are selected to mature or die through the interaction with thymic stromal cells. To establish the immunological self in the thymus, medullary thymic epithelial cells (mTECs) express diverse sets of tissue-specific self-antigens (TSAs). This ectopic expression of TSAs largely depends on the transcriptional regulator Aire, yet the mechanism controlling Aire expression itself remains unknown. Here, we show that Jmjd6, a dioxygenase that catalyses lysyl hydroxylation of splicing regulatory proteins, is critical for Aire expression...
2015: Nature Communications
Jianhao Wang, Jinchen Li, Jianpeng Wang, Cheli Wang, Tiwan Teng, Yao Chen, Jinping Li, Bingyu Dong, Lin Qiu, Pengju Jiang
Nanoparticles provide significantly enhanced binding characteristics. However, fast online probing of the self-assembly process remains hard to achieve in practice. Herein, we report a fluorescence coupled CE method for probing the self-assembly events between quantum dots (QDs) and engineered Jumonji domain-containing protein 6 (Jmjd6) enzyme. QDs and Jmjd6 were sequentially injected into the capillary, where the self-assembly took place in a nanoliter scale. In particular, we showed that the Jmjd6/QD ratio, the interval time, and the injection volume had a great effect on the online self-assembly...
February 2016: Electrophoresis
Irina Tikhanovich, Sudhakiranmayi Kuravi, Antonio Artigues, Maria T Villar, Kenneth Dorko, Atta Nawabi, Benjamin Roberts, Steven A Weinman
Arginine methylation is a common post-translational modification, but its role in regulating protein function is poorly understood. This study demonstrates that, TNF receptor-associated factor 6 (TRAF6), an E3 ubiquitin ligase involved in innate immune signaling, is regulated by reversible arginine methylation in a range of primary and cultured cells. Under basal conditions, TRAF6 is methylated by the methyltransferase PRMT1, and this inhibits its ubiquitin ligase activity, reducing activation of toll-like receptor signaling...
September 4, 2015: Journal of Biological Chemistry
Xuena Zhang, Yan Gao, Lei Lu, Zan Zhang, Shengchun Gan, Liyang Xu, Anhua Lei, Ying Cao
Tcf7l1 (also known as Tcf3) is a bimodal transcription factor that plays essential roles in embryogenesis and embryonic and adult stem cells. On one hand, Tcf7l1 works as transcriptional repressor via the recruitment of Groucho-related transcriptional corepressors to repress the transcription of Wnt target genes, and, on the other hand, it activates Wnt target genes when Wnt-activated β-catenin interacts with it. However, how its activity is modulated is not well understood. Here we demonstrate that a JmjC-domain containing protein, Jmjd6, interacts with Tcf7l and derepresses Tcf7l...
August 14, 2015: Journal of Biological Chemistry
Yong Huang, Donghong Chen, Chunlin Liu, Wenhui Shen, Ying Ruan
Histone modification regulates plant development events by epigenetically silencing or activating gene expression, and histone methylation is regulated by histone lysine methyltransferases (KMTs) and histone lysine demethylases (KDMs). The JmjC domain proteins, an important KDM family, erase methyl marks (CH3-) from histones and play key roles in maintaining homeostasis of histone methylation in vivo. Here, we analyzed 169 JmjC domain proteins from whole genomes of plants ranging from green alga to higher plants together with 36 from two animals (fruit fly and human)...
February 2016: Molecular Genetics and Genomics: MGG
Tsu-Fang Wu, Ya-Li Yao, I-Lu Lai, Chien-Chen Lai, Pei-Lun Lin, Wen-Ming Yang
PAX3 is a transcription factor critical to gene regulation in mammalian development. Mutations in PAX3 are associated with Waardenburg syndrome (WS), but the mechanism of how mutant PAX3 proteins cause WS remains unclear. Here, we found that PAX3 loads on mitotic chromosomes using its homeodomain. PAX3 WS mutants with mutations in homeodomain lose the ability to bind mitotic chromosomes. Moreover, loading of PAX3 on mitotic chromosomes requires arginine methylation, which is regulated by methyltransferase PRMT5 and demethylase JMJD6...
August 14, 2015: Journal of Biological Chemistry
Yu-Jie Hu, Houda Belaghzal, Wen-Yu Hsiao, Jun Qi, James E Bradner, David A Guertin, Saïd Sif, Anthony N Imbalzano
Jumonji domain-containing protein 6 (JMJD6) is a nuclear protein involved in histone modification, transcription and RNA processing. Although JMJD6 is crucial for tissue development, the link between its molecular functions and its roles in any given differentiation process is unknown. We report that JMJD6 is required for adipogenic gene expression and differentiation in a manner independent of Jumonji C domain catalytic activity. JMJD6 knockdown led to a reduction of C/EBPβ and C/EBPδ protein expression without affecting mRNA levels in the early phase of differentiation...
September 18, 2015: Nucleic Acids Research
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