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https://www.readbyqxmd.com/read/27715397/depletion-of-jmjd5-sensitizes-tumor-cells-to-microtubule-destabilizing-agents-by-altering-microtubule-stability
#1
Junyu Wu, Zhimin He, Da-Liang Wang, Fang-Lin Sun
Microtubules play essential roles in mitosis, cell migration, and intracellular trafficking. Drugs that target microtubules have demonstrated great clinical success in cancer treatment due to their capacity to impair microtubule dynamics in both mitotic and interphase stages. In a previous report, we demonstrated that JMJD5 associated with mitotic spindle and was required for proper mitosis. However, it remains elusive whether JMJD5 could regulate the stability of cytoskeletal microtubules and whether it affects the efficacy of microtubule-targeting agents...
November 2016: Cell Cycle
https://www.readbyqxmd.com/read/27086112/cold-dependent-alternative-splicing-of-a-jumonji-c-domain-containing-gene-mtjmjc5-in-medicago-truncatula
#2
Yingfang Shen, Xiaopei Wu, Demei Liu, Shengjing Song, Dengcai Liu, Haiqing Wang
Histone methylation is an epigenetic modification mechanism that regulates gene expression in eukaryotic cells. Jumonji C domain-containing demethylases are involved in removal of methyl groups at lysine or arginine residues. The JmjC domain-only member, JMJ30/JMJD5 of Arabidopsis, is a component of the plant circadian clock. Although some plant circadian clock genes undergo alternative splicing in response to external cues, there is no evidence that JMJ30/JMJD5 is regulated by alternative splicing. In this study, the expression of an Arabidopsis JMJ30/JMJD5 ortholog in Medicago truncatula, MtJMJC5, in response to circadian clock and abiotic stresses were characterized...
May 27, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/26792738/hepatocyte-factor-jmjd5-regulates-hepatitis-b-virus-replication-through-interaction-with-hbx
#3
Takahisa Kouwaki, Toru Okamoto, Ayano Ito, Yukari Sugiyama, Kazuo Yamashita, Tatsuya Suzuki, Shinji Kusakabe, Junki Hirano, Takasuke Fukuhara, Atsuya Yamashita, Kazunobu Saito, Daisuke Okuzaki, Koichi Watashi, Masaya Sugiyama, Sachiyo Yoshio, Daron M Standley, Tatsuya Kanto, Masashi Mizokami, Kohji Moriishi, Yoshiharu Matsuura
UNLABELLED: Hepatitis B virus (HBV) is a causative agent for chronic liver diseases such as hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). HBx protein encoded by the HBV genome plays crucial roles not only in pathogenesis but also in replication of HBV. Although HBx has been shown to bind to a number of host proteins, the molecular mechanisms by which HBx regulates HBV replication are largely unknown. In this study, we identified jumonji C-domain-containing 5 (JMJD5) as a novel binding partner of HBx interacting in the cytoplasm...
April 2016: Journal of Virology
https://www.readbyqxmd.com/read/26760772/epigenetic-silencing-of-jmjd5-promotes-the-proliferation-of-hepatocellular-carcinoma-cells-by-down-regulating-the-transcription-of-cdkn1a-686
#4
Bing-Hao Wu, Hui Chen, Chun-Miao Cai, Jia-Zhu Fang, Chong-Chao Wu, Li-Yu Huang, Lan Wang, Ze-Guang Han
Proteins that contain jumonji C (JmjC) domains have recently been identified as major contributors to various malignant human cancers through epigenetic remodeling. However, the roles of these family members in the pathogenesis of hepatocellular carcinoma (HCC) are obscure. By mining public databases, we found that the HCC patients with lower JmjC domain-containing protein 5 (JMJD5) expression exhibited shorter survival time. We then confirmed that JMJD5 expression was indeed decreased in HCC specimens, which was caused by the altered epigenetic histone modifications, the decreased H3K9ac, H3K27ac and H3K4me2/3 together with the increased trimethylation of H3K27 and H3K9 on the JMJD5 promoter...
February 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/26710852/jmjd5-jumonji-domain-containing-5-associates-with-spindle-microtubules-and-is-required-for-proper-mitosis
#5
Zhimin He, Junyu Wu, Xiaonan Su, Ye Zhang, Lixia Pan, Huimin Wei, Qiang Fang, Haitao Li, Da-Liang Wang, Fang-Lin Sun
Precise mitotic spindle assembly is a guarantee of proper chromosome segregation during mitosis. Chromosome instability caused by disturbed mitosis is one of the major features of various types of cancer. JMJD5 has been reported to be involved in epigenetic regulation of gene expression in the nucleus, but little is known about its function in mitotic process. Here we report the unexpected localization and function of JMJD5 in mitotic progression. JMJD5 partially accumulates on mitotic spindles during mitosis, and depletion of JMJD5 results in significant mitotic arrest, spindle assembly defects, and sustained activation of the spindle assembly checkpoint (SAC)...
February 26, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/26617740/overexpression-of-histone-demethylase-jmjd5-promotes-metastasis-and-indicates-a-poor-prognosis-in-breast-cancer
#6
Zhihua Zhao, Chuntao Sun, Fengqi Li, Jiankui Han, Xanjun Li, Zhenguo Song
In this study, we showed the expression of JMJD5 was increased in breast cancer tissues and breast adenocarcinoma cell lines MCF-7 as well as triple negative breast cancer cell lines MDA-MB-231 compared with paired adjacent normal mammary tissues and normal mammary epithelial cell lines MCF-10A. The higher expression of JMJD5 was significantly corresponded with clinical stage, histological grade and lymph node metastasis. Overexpression of JMJD5 promoted cell invasion and induce EMT, while JMJD5 siRNA inhibits MDA-MB-231 cells invasion in vitro...
2015: International Journal of Clinical and Experimental Pathology
https://www.readbyqxmd.com/read/26334721/jmjd5-functions-as-a-regulator-of-p53-signaling-during-mouse-embryogenesis
#7
Akihiko Ishimura, Minoru Terashima, Shoichiro Tange, Takeshi Suzuki
Genetic studies have shown that aberrant activation of p53 signaling leads to embryonic lethality. Maintenance of a fine balance of the p53 protein level is critical for normal development. Previously, we have reported that Jmjd5, a member of the Jumonji C (JmjC) family, regulates embryonic cell proliferation through the control of Cdkn1a expression. Since Cdkn1a is the representative p53-regulated gene, we have examined whether the expression of other p53 target genes is coincidentally upregulated with Cdkn1a in Jmjd5-deficient embryos...
March 2016: Cell and Tissue Research
https://www.readbyqxmd.com/read/26261525/jmjd5-is-a-potential-oncogene-for-colon-carcinogenesis
#8
Ru Zhang, Qingjun Huang, Yinpeng Li, Yang Song, Yingxue Li
OBJECTIVE: To observe the effects of Jumonji C domain-containing (JMJD) 5 depletion on colon cancer (CC). METHODS: A short-hairpin RNA targeting JMJD5 was transfected into a lentivirus to make Lv-shJMJD5 for infection into the Caco-2 human cell. Besides, a negative control shRNA was constructed. The mRNA and protein levels of JMJD5 were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting, respectively. Cell proliferation, migration, and invasion were assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), soft agar colony assay and transwell assay, respectively...
2015: International Journal of Clinical and Experimental Pathology
https://www.readbyqxmd.com/read/26240495/epigenetic-role-of-histone-3-lysine-methyltransferase-and-demethylase-in-regulating-apoptosis-predicting-the-recurrence-of-atypical-meningioma
#9
Sang Hyuk Lee, Eun Hee Lee, Sung-Hun Lee, Young Min Lee, Hyung Dong Kim, Young Zoon Kim
Alteration of apoptosis is related with progression and recurrence of atypical meningiomas (AMs). However, no comprehensive study has been conducted regarding histone modification regulating apoptosis in AMs. This study aimed to determine the prognostic values of certain apoptosis-associated factors, and examine the role of histone modification on apoptosis in AMs. The medical records of 67 patients with AMs, as diagnosed during recent 13 yr, were reviewed retrospectively. Immunohistochemical staining was performed on archived paraffin-embedded tissues for pro-apoptotic factors (CASP3, IGFBP, TRAIL-R1, BAX, and XAF1), anti-apoptotic factors (survivin, ERK, RAF1, MDM2, and BCL2), and the histone modifying enzymes (MLL2, RIZ, EZH1, NSD2, KDM5c, JMJD2a, UTX, and JMJD5)...
August 2015: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/26025680/jmjd5-interacts-with-p53-and-negatively-regulates-p53-function-in-control-of-cell-cycle-and-proliferation
#10
Xiaobin Huang, Shuilian Zhang, Hongyan Qi, Zhengyang Wang, Hong-Wu Chen, Jimin Shao, Jing Shen
JMJD5 is a Jumonji C domain-containing demethylase/hydroxylase shown to be essential in embryological development, osteoclastic maturation, circadian rhythm regulation and cancer metabolism. However, its role and underlying mechanisms in oncogenesis remain unclear. Here, we demonstrate that JMJD5 forms complex with the tumor suppressor p53 by interacting with p53 DNA-binding domain (DBD), and negatively regulates its activity. Downregulation of JMJD5 resulted in increased expression of multiple p53 downstream genes, such as the cell cycle inhibitor CDKN1A and DNA repair effector P53R2, only in p53-proficient lung cancer cells...
October 2015: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/25463925/the-histone-demethylase-fbxl11-kdm2a-plays-an-essential-role-in-embryonic-development-by-repressing-cell-cycle-regulators
#11
Eri Kawakami, Akinori Tokunaga, Manabu Ozawa, Reiko Sakamoto, Nobuaki Yoshida
Methylation and de-methylation of histone lysine residues play pivotal roles in mammalian early development; these modifications influence chromatin architecture and regulate gene transcription. Fbxl11 (F-box and leucine-rich repeat 11)/Kdm2a is a histone demethylase that selectively removes mono- and di-methylation from histone H3K36. Previously, two other histone H3K36 demethylases (Jmjd5 or Fbxl10) were analyzed based on the phenotypes of the corresponding knockout (KO) mice; the results of those studies implicated H3K36 demethylases in cell proliferation, apoptosis, and senescence (Fukuda et al...
February 2015: Mechanisms of Development
https://www.readbyqxmd.com/read/24740926/jmjd5-regulates-cell-cycle-and-pluripotency-in-human-embryonic-stem-cells
#12
Hui Zhu, Shijun Hu, Julie Baker
In mammalian embryos, embryonic stem cells (ESCs) and induced pluripotent cells, a shortened G1 phase is correlated with the pluripotent state. To molecularly define this phase, we compared transcripts from the shortened G1 of human ESCs (hESCs) with those from the longer G1 of derived endoderm. We identified JMJD5, a JmjC (Jumonji C) domain containing protein that, when depleted in hESCs, causes the accumulation of cells in G1 phase, loss of pluripotency, and subsequent differentiation into multiple lineages, most prominently ectoderm and trophectoderm...
August 2014: Stem Cells
https://www.readbyqxmd.com/read/24735454/cell-type-specific-jumonji-histone-demethylase-gene-expression-in-the-healthy-rat-cns-detection-by-a-novel-flow-cytometry-method
#13
Stephanie M C Smith, Rebecca S Kimyon, Jyoti J Watters
Our understanding of how histone demethylation contributes to the regulation of basal gene expression in the brain is largely unknown in any injury model, and especially in the healthy adult brain. Although Jumonji genes are often regulated transcriptionally, cell-specific gene expression of Jumonji histone demethylases in the brain remains poorly understood. Thus, in the present study we profiled the mRNA levels of 26 Jumonji genes in microglia (CD11b+), neurons (NeuN+) and astrocytes (GFAP+) from the healthy adult rat brain...
2014: ASN Neuro
https://www.readbyqxmd.com/read/24344305/jmjd5-regulates-pkm2-nuclear-translocation-and-reprograms-hif-1%C3%AE-mediated-glucose-metabolism
#14
Hung-Jung Wang, Ya-Ju Hsieh, Wen-Chi Cheng, Chun-Pu Lin, Yu-shan Lin, So-Fang Yang, Chung-Ching Chen, Yoshihiro Izumiya, Jau-Song Yu, Hsing-Jien Kung, Wen-Ching Wang
JMJD5, a Jumonji C domain-containing dioxygenase, is important for embryonic development and cancer growth. Here, we show that JMJD5 is up-regulated by hypoxia and is crucial for hypoxia-induced cell proliferation. JMJD5 interacts directly with pyruvate kinase muscle isozyme (PKM)2 to modulate metabolic flux in cancer cells. The JMJD5-PKM2 interaction resides at the intersubunit interface region of PKM2, which hinders PKM2 tetramerization and blocks pyruvate kinase activity. This interaction also influences translocation of PKM2 into the nucleus and promotes hypoxia-inducible factor (HIF)-1α-mediated transactivation...
January 7, 2014: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/24100311/structure-of-the-jmjc-domain-containing-protein-jmjd5
#15
Haipeng Wang, Xing Zhou, Minhao Wu, Chengliang Wang, Xiaoqin Zhang, Yue Tao, Nini Chen, Jianye Zang
The post-translational modification of histone tails is the principal process controlling epigenetic regulation in eukaryotes. The lysine methylation of histones is dynamically regulated by two distinct classes of enzymes: methyltransferases and demethylases. JMJD5, which plays an important role in cell-cycle progression, circadian rhythms and embryonic cell proliferation, has been shown to be a JmjC-domain-containing histone demethylase with enzymatic activity towards H3K36me2. Here, the crystal structure of human JMJD5 lacking the N-terminal 175 amino-acid residues is reported...
October 2013: Acta Crystallographica. Section D, Biological Crystallography
https://www.readbyqxmd.com/read/23948433/identification-and-functional-implication-of-nuclear-localization-signals-in-the-n-terminal-domain-of-jmjd5
#16
Xiaobin Huang, Lingna Zhang, Hongyan Qi, Jimin Shao, Jing Shen
JMJD5 has recently been reported to participate in circadian rhythm regulation, embryological development, osteoclastogenesis and tumorigenesis. Although JMJD5 has been found mainly localized in the nucleus of cells, how it enters the nucleus remains unclear. Here we report that JMJD5 contains a functional bipartite nuclear localization signal (NLS) and a chromosome region maintenance 1 (CRM1)-dependent nuclear export signal (NES). Importin α/β and transportin-1 were further identified as JMJD5-associated transport proteins, and different binding regions were determined for the two nuclear import receptors...
November 2013: Biochimie
https://www.readbyqxmd.com/read/22851697/crystal-structure-and-functional-analysis-of-jmjd5-indicate-an-alternate-specificity-and-function
#17
Paul A Del Rizzo, Swathi Krishnan, Raymond C Trievel
JMJD5 is a Jumonji C (JmjC) protein that has been implicated in breast cancer tumorigenesis, circadian rhythm regulation, embryological development, and osteoclastogenesis. Recently, JMJD5 (also called KDM8) has been reported to demethylate dimethylated Lys-36 in histone H3 (H3K36me2), regulating genes that control cell cycle progression. Here, we report high-resolution crystal structures of the human JMJD5 catalytic domain in complex with the substrate 2-oxoglutarate (2-OG) and the inhibitor N-oxalylglycine (NOG)...
October 2012: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/22402282/histone-demethylase-jmjd5-is-essential-for-embryonic-development
#18
Sangphil Oh, Ralf Janknecht
Histone lysine methylation is pivotal in regulating chromatin structure and thus profoundly affects the transcriptome. JMJD5 (jumonji C domain-containing 5) is a histone demethylase that specifically removes methyl moieties from dimethylated lysine 36 on histone H3 and exerts a pro-proliferative effect on breast cancer cells. Here, we generated JMJD5 knockout mice in order to study the physiological significance of this enzyme. Whereas heterozygous knockout mice displayed no overt phenotype, homozygous JMJD5 knockouts died around day 10 of embryonal development...
March 30, 2012: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/22375008/jmjd5-a-jumonji-c-jmjc-domain-containing-protein-negatively-regulates-osteoclastogenesis-by-facilitating-nfatc1-protein-degradation
#19
Min-Young Youn, Atsushi Yokoyama, Sally Fujiyama-Nakamura, Fumiaki Ohtake, Ken-ichi Minehata, Hisataka Yasuda, Takeshi Suzuki, Shigeaki Kato, Yuuki Imai
Osteoclastogenesis is a highly regulated process governed by diverse classes of regulators. Among them, nuclear factor of activated T-cells calcineurin-dependent 1 (NFATc1) is the primary osteoclastogenic transcription factor, and its expression is transcriptionally induced during early osteoclastogenesis by receptor activation of nuclear factor κB ligand (RANKL), an osteoclastogenic cytokine. Here, we report the novel enzymatic function of JMJD5, which regulates NFATc1 protein stability. Among the tested Jumonji C (JmjC) domain-containing proteins, decreased mRNA expression levels during osteoclastogenesis were found for JMJD5 in RAW264 cells stimulated by RANKL...
April 13, 2012: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/22326748/differential-proteome-profiling-of-pleural-effusions-from-lung-cancer-and-benign-inflammatory-disease-patients
#20
COMPARATIVE STUDY
Zhengyang Wang, Cheng Wang, Xiaobin Huang, Ying Shen, Jing Shen, Kejing Ying
The pleural effusion proteome has been found containing information that directly reflects pathophysiological status and represents a potential diagnostic value for pulmonary diseases. However, the variability in protein composition between malignant and benign effusions is not well understood. Herein, we investigated the changes of proteins in pleural effusions from lung adenocarcinoma and benign inflammatory disease (pneumonia and tuberculosis) patients by two-dimensional difference gel electrophoresis (2D-DIGE)...
April 2012: Biochimica et Biophysica Acta
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