Read by QxMD icon Read


Shuai Huang, Aruna Balgi, Yaping Pan, Meng Li, Xiaoran Zhang, Lilin Du, Ming Zhou, Michel Roberge, Xin Li
Nucleotide-binding leucine-rich repeat (NLR) proteins serve as immune receptors in both plants and animals. To identify components required for NLR-mediated immunity, we designed and carried out a chemical genetics screen to search for small molecules that can alter resistance responses in Arabidopsis thaliana. From 13,600 compounds, we identified Ro 8-4304 that is able to specifically suppress the severe autoimmune phenotypes of chs3-2D (chilling sensitive 3, 2D), including the arrested growth morphology and heightened PR (Pathogenesis Related) gene expression...
October 15, 2016: Molecular Plant
Sen Ji, Shuang Ma, Wen-Jing Wang, Shen-Zhen Huan, Tian-Qi Wang, Rong Xiang, Yi-Guo Hu, Qiang Chen, Lin-Li Li, Sheng-Yong Yang
PRMT5 is an important protein arginine methyltransferase that catalyzes the symmetric dimethylation of arginine resides on histones or non-histone substrate proteins. It has been thought as a promising target for many diseases, particularly cancer. Despite the potential applications of PRMT5 inhibitors in cancer treatment, very few of PRMT5i have been publicly reported. In this investigation, virtual screening and structure-activity relationship (SAR) studies were carried out to discovery novel PRMT5i, which finally led to the identification of a number of new PRMT5i...
October 7, 2016: Chemical Biology & Drug Design
Hao Yang, Xiaoping Zhao, Li Zhao, Liu Liu, Jiajin Li, Wenzhi Jia, Jianjun Liu, Gang Huang
Although cancer cells are known to be "addicted" to glucose, the effect of glucose in proliferation of these cells remains elusive. Here, we report that upon glucose induction, protein arginine methyltransferase 5 (PRMT5) exerts a profound effect on the G1-S cell cycle progression via directly interacting with cyclin dependent kinase 4 (CDK4) in hepatocellular carcinoma (HCC). Upregulation of both PRMT5 and CDK4 predicts more malignant characteristics in human HCC tissues. Mechanistically, glucose promotes the interaction between PRMT5 and CDK4, which leads to activation of CDK4-RB-E2F-mediated transcription via releasing CDKN2A from CDK4...
September 30, 2016: Oncotarget
Yanli Jin, Jingfeng Zhou, Fang Xu, Bei Jin, Lijing Cui, Yun Wang, Xin Du, Juan Li, Peng Li, Ruibao Ren, Jingxuan Pan
Imatinib-insensitive leukemia stem cells (LSCs) are believed to be responsible for resistance to BCR-ABL tyrosine kinase inhibitors and relapse of chronic myelogenous leukemia (CML). Identifying therapeutic targets to eradicate CML LSCs may be a strategy to cure CML. In the present study, we discovered a positive feedback loop between BCR-ABL and protein arginine methyltransferase 5 (PRMT5) in CML cells. Overexpression of PRMT5 was observed in human CML LSCs. Silencing PRMT5 with shRNA or blocking PRMT5 methyltransferase activity with the small-molecule inhibitor PJ-68 reduced survival, serial replating capacity, and long-term culture-initiating cells (LTC-ICs) in LSCs from CML patients...
October 3, 2016: Journal of Clinical Investigation
Wei-Chih Tsai, Sitaram Gayatri, Lucas C Reineke, Gianluca Sbardella, Mark T Bedford, Richard E Lloyd
Stress granules (SGs) are cytoplasmic condensates of stalled messenger ribonucleoprotein complexes (mRNPs) that form when eukaryotic cells encounter environmental stress. RNA binding proteins are enriched for arginine methylation and facilitate SG assembly through interactions involving regions of low amino acid complexity. How methylation of specific RNA binding proteins regulates RNA granule assembly has not been characterized. Here, we examined the potent SG nucleating protein Ras-GAP SH3 Binding Protein 1 (G3BP1), and found that G3BP1 is differentially methylated on specific arginine residues by protein arginine methyltransferase (PRMT) 1 and PRMT5 in its RGG domain...
September 6, 2016: Journal of Biological Chemistry
Sara C Larsen, Kathrine B Sylvestersen, Andreas Mund, David Lyon, Meeli Mullari, Maria V Madsen, Jeremy A Daniel, Lars J Jensen, Michael L Nielsen
The posttranslational modification of proteins by arginine methylation is functionally important, yet the breadth of this modification is not well characterized. Using high-resolution mass spectrometry, we identified 8030 arginine methylation sites within 3300 human proteins in human embryonic kidney 293 cells, indicating that the occurrence of this modification is comparable to phosphorylation and ubiquitylation. A site-level conservation analysis revealed that arginine methylation sites are less evolutionarily conserved compared to arginines that were not identified as modified by methylation...
2016: Science Signaling
X Deng, G Shao, H-T Zhang, C Li, D Zhang, L Cheng, B D Elzey, R Pili, T L Ratliff, J Huang, C-D Hu
Protein arginine methyltransferase 5 (PRMT5) is an emerging epigenetic enzyme that mainly represses transcription of target genes via symmetric dimethylation of arginine residues on histones H4R3, H3R8 and H2AR3. Accumulating evidence suggests that PRMT5 may function as an oncogene to drive cancer cell growth by epigenetic inactivation of several tumor suppressors. Here, we provide evidence that PRMT5 promotes prostate cancer cell growth by epigenetically activating transcription of the androgen receptor (AR) in prostate cancer cells...
August 22, 2016: Oncogene
Wei Du, Surya Amarachintha, Ozlem Erden, Andrew Wilson, Qishen Pang
The Fanconi anemia (FA) pathway is involved in DNA damage and other cellular stress responses. We have investigated the role of the FA pathway in oncogenic stress response by employing an in vivo stress-response model expressing the Gadd45β-luciferase transgene. Using two inducible models of oncogenic activation (LSL-K-rasG12D and MycER), we show that hematopoietic stem and progenitor cells (HSPCs) from mice deficient for the FA core complex components Fanca or Fancc exhibit aberrant short-lived response to oncogenic insults...
August 5, 2016: Oncotarget
Fabio Marino, Geert P M Mommen, Anita Jeko, Hugo D Meiring, Jacqueline A M van Gaans-van den Brink, Richard Alexander Scheltema, Cecile A C M van Els, Albert J R Heck
Alterations in protein post-translational modification (PTMs) are recognized hallmarks of diseases. These modifications potentially provide a unique source of disease-related Human Leukocyte Antigen (HLA) class I-presented peptides that can elicit specific immune responses. While phosphorylated HLA peptides have already received attention, arginine methylated HLA class I peptide presentation has not been characterized in detail. In a human B-cell line we detected 149 HLA class I peptides harboring mono- and/or di-methylated arginine residues by mass spectrometry...
August 8, 2016: Journal of Proteome Research
Xiao-Li Zhang, Jun Wu, Jian Wang, Tingting Shen, Hua Li, Jun Lu, Yunzhao Gu, Yani Kang, Chee-Hong Wong, Chew Yee Ngan, Zhifeng Shao, Ji Wu, Xiaodong Zhao
BACKGROUND: Germline stem cells play an essential role in establishing the fertility of an organism. Although extensively characterized, the regulatory mechanisms that govern the fundamental properties of mammalian female germline stem cells remain poorly understood. RESULTS: We generate genome-wide profiles of the histone modifications H3K4me1, H3K27ac, H3K4me3, and H3K27me3, DNA methylation, and RNA polymerase II occupancy and perform transcriptome analysis in mouse female germline stem cells...
2016: Genome Biology
Suresh Ambati, Ping Yu, Elizabeth C McKinney, Muthugapatti K Kandasamy, Diane Hartzell, Clifton A Baile, Richard B Meagher
BACKGROUND: Obesity-related comorbidities are thought to result from the reprogramming of the epigenome in numerous tissues and cell types, and in particular, mature adipocytes within visceral and subcutaneous adipose tissue, VAT and SAT. The cell-type specific chromatin remodeling of mature adipocytes within VAT and SAT is poorly understood, in part, because of the difficulties of isolating and manipulating large fragile mature adipocyte cells from adipose tissues. METHODS: We constructed MA-INTACT (Mature Adipocyte-Isolation of Nuclei TAgged in specific Cell Types) mice using the adiponectin (ADIPOQ) promoter (ADNp) to tag the surface of mature adipocyte nuclei with a reporter protein...
2016: BMC Obesity
Blair R McCallie, Jason C Parks, Alyssa L Patton, Darren K Griffin, William B Schoolcraft, Mandy G Katz-Jaffe
DNA methylation is a key epigenetic mechanism responsible for gene regulation, chromatin remodeling, and genome stability, playing a fundamental role during embryonic development. The aim of this study was to determine if these epigenetic marks are associated with chromosomal aneuploidy in human blastocysts. Surplus, cryopreserved blastocysts that were donated to research with IRB consent were chosen with varying chromosomal aneuploidies and respective implantation potential: monosomies and trisomies 7, 11, 15, 21, and 22...
2016: PloS One
Yinshan Bai, Meiying Feng, Shanshan Liu, Hengxi Wei, Li Li, Xianwei Zhang, Chao Shen, Shouquan Zhang, Ningfang Ma
Mouse spermatogonial stem cells (mSSCs) may be reprogrammed to become pluripotent stem cells under in vitro culture conditions, due to epigenetic modifications, which are closely associated with the expression of transcription factors and epigenetic factors. Thus, this study was conducted to compare the gene expression of transcription factors and epigenetic factors in mSSCs and mouse embryonic stem cells (mESCs). Firstly, the freshly isolated mSSCs [mSSCs (f)] were enriched by magnetic-activated cell sorting with Thy1...
August 2016: International Journal of Molecular Medicine
Mitsuro Kanda, Dai Shimizu, Tsutomu Fujii, Haruyoshi Tanaka, Masahiro Shibata, Naoki Iwata, Masamichi Hayashi, Daisuke Kobayashi, Chie Tanaka, Suguru Yamada, Goro Nakayama, Hiroyuki Sugimoto, Masahiko Koike, Michitaka Fujiwara, Yasuhiro Kodera
Identification of novel gastric cancer (GC)-related molecules is necessary to improve management of patients with GC in both diagnostic and therapeutic aspects. The aim of the present study was to determine whether protein arginine methyltransferase 5 (PRMT5) acts as an oncogene in the progression of GC and whether it serves as a novel diagnostic marker and therapeutic target. We conducted global expression profiling of GC cell lines and RNA interference experiments to evaluate the effect of PRMT5 expression on the phenotype of GC cells...
September 2016: International Journal of Oncology
Y K Banasavadi-Siddegowda, L Russell, E Frair, V A Karkhanis, T Relation, J Y Yoo, J Zhang, S Sif, J Imitola, R Baiocchi, B Kaur
Glioblastoma (GBM) represents the most common and aggressive histologic subtype among malignant astrocytoma and is associated with poor outcomes because of heterogeneous tumour cell population including mature non-stem-like cell and immature stem-like cells within the tumour. Thus, it is critical to find new target-specific therapeutic modalities. Protein arginine methyltransferase enzyme 5 (PRMT5) regulates many cellular processes through its methylation activity and its overexpression in GBM is associated with more aggressive disease...
June 13, 2016: Oncogene
H Chen, B Lorton, V Gupta, D Shechter
Protein arginine methyltransferase 5 (PRMT5) complexed with MEP50/WDR77 catalyzes arginine methylation on histones and other proteins. PRMT5-MEP50 activity is elevated in cancer cells and its expression is highly correlated with poor prognosis in many human tumors. We demonstrate that PRMT5-MEP50 is essential for transcriptional regulation promoting cancer cell invasive phenotypes in lung adenocarcinoma, lung squamous cell carcinoma and breast carcinoma cancer cells. RNA-Seq transcriptome analysis demonstrated that PRMT5 and MEP50 are required to maintain expression of metastasis and Epithelial-to-mesenchymal transition (EMT) markers and to potentiate an epigenetic mechanism of the TGFβ response...
June 6, 2016: Oncogene
Marcos Arribas-Layton, Jaclyn Dennis, Eric J Bennett, Christian K Damgaard, Jens Lykke-Andersen
Processing bodies (PBs) are conserved cytoplasmic aggregations of translationally repressed mRNAs assembled with mRNA decay factors. The aggregation of mRNA-protein (mRNP) complexes into PBs involves interactions between low-complexity regions of protein components of the mRNPs. In Saccharomyces cerevisiae, the carboxy (C)-terminal Q/N-rich domain of the Lsm4 subunit of the Lsm1-7 complex plays an important role in PB formation, but the C-terminal domain of Lsm4 in most eukaryotes is an RGG domain rather than Q/N rich...
September 1, 2016: Molecular and Cellular Biology
Md Sajid Ghufran, Krishna Ghosh, Santosh R Kanade
The exposure of naturally occurring mycotoxins affects human health and play a vital role in cancer initiation and progression. Aflatoxin B1 is a difuranocoumarin mycotoxin, classified as a group I carcinogen. The present study was conducted to assess the effect of aflatoxin B1 on epigenetic regulatory proteins. The protein arginine methyltransferase 5 expression was induced upon aflatoxin B1 treatment in a dose and time dependent manner. Further global arginine methylation was also increased in the same manner...
September 1, 2016: Toxicon: Official Journal of the International Society on Toxinology
Zineb Mounir, Joshua M Korn, Thomas Westerling, Fallon Lin, Christina A Kirby, Markus Schirle, Gregg McAllister, Greg Hoffman, Nadire Ramadan, Anke Hartung, Yan Feng, David Randal Kipp, Christopher Quinn, Michelle Fodor, Jason Baird, Marie Schoumacher, Ronald Meyer, James Deeds, Gilles Buchwalter, Travis Stams, Nicholas Keen, William R Sellers, Myles Brown, Raymond A Pagliarini
The TMPRSS2:ERG gene fusion is common in androgen receptor (AR) positive prostate cancers, yet its function remains poorly understood. From a screen for functionally relevant ERG interactors, we identify the arginine methyltransferase PRMT5. ERG recruits PRMT5 to AR-target genes, where PRMT5 methylates AR on arginine 761. This attenuates AR recruitment and transcription of genes expressed in differentiated prostate epithelium. The AR-inhibitory function of PRMT5 is restricted to TMPRSS2:ERG-positive prostate cancer cells...
2016: ELife
Eun-Kyung Moon, Yeonchul Hong, Dong-Il Chung, Youn-Kyoung Goo, Hyun-Hee Kong
Encystation is an essential process for Acanthamoeba survival under nutrient-limiting conditions and exposure to drugs. The expression of several genes has been observed to increase or decrease during encystation. Epigenetic processes involved in regulation of gene expression have been shown to play a role in several pathogenic parasites. In the present study, we identified the protein arginine methyltransferase 5 (PRMT5), a known epigenetic regulator, in Acanthamoeba castellanii. PRMT5 of A. castellanii (AcPRMT5) contained domains found in S-adenosylmethionine-dependent methyltransferases and in PRMT5 arginine-N-methyltransferase...
April 2016: Korean Journal of Parasitology
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"