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https://www.readbyqxmd.com/read/28537268/global-mapping-of-carm1-substrates-defines-enzyme-specificity-and-substrate-recognition
#1
Evgenia Shishkova, Hao Zeng, Fabao Liu, Nicholas W Kwiecien, Alexander S Hebert, Joshua J Coon, Wei Xu
Protein arginine methyltransferases (PRMTs) introduce arginine methylation, a post-translational modification with the increasingly eminent role in normal physiology and disease. PRMT4 or coactivator-associated arginine methyltransferase 1 (CARM1) is a propitious target for cancer therapy; however, few CARM1 substrates are known, and its mechanism of substrate recognition is poorly understood. Here we employed a quantitative mass spectrometry approach to globally profile CARM1 substrates in breast cancer cell lines...
May 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28455686/flightless-i-homolog-regulates-glucocorticoid-receptor-mediated-transcription-via-direct-interaction-of-the-leucine-rich-repeat-domain
#2
Hong Lan Jin, Liu Yang, Kwang Won Jeong
Flightless-I homolog (FLII) is a member of the gelsolin family of proteins, and has been identified as a coactivator of estrogen receptor-mediated transcription. Here, we investigate the role of FLII in the glucocorticoid receptor (GR) signaling pathway. Reporter gene assay and real-time quantitative PCR in A549 were performed to investigate the function of FLII in the expression of GR target genes. Co-immunoprecipitation assay and in vitro binding assay were used to identify binding domain of FLII. Chromatin immunoprecipitation assay were carried out with FLII-depleted A549 cells to determine the role of FLII at GR binding sites...
April 28, 2017: Molecular Biology Reports
https://www.readbyqxmd.com/read/28432361/disease-biomarker-identification-from-gene-network-modules-for-metastasized-breast-cancer
#3
Pooja Sharma, Dhruba K Bhattacharyya, Jugal Kalita
Advancement in science has tended to improve treatment of fatal diseases such as cancer. A major concern in the area is the spread of cancerous cells, technically refered to as metastasis into other organs beyond the primary organ. Treatment in such a stage of cancer is extremely difficult and usually palliative only. In this study, we focus on finding gene-gene network modules which are functionally similar in nature in the case of breast cancer. These modules extracted during the disease progression stages are analyzed using p-value and their associated pathways...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28330993/transition-state-mimics-are-valuable-mechanistic-probes-for-structural-studies-with-the-arginine-methyltransferase-carm1
#4
Matthijs J van Haren, Nils Marechal, Nathalie Troffer-Charlier, Agostino Cianciulli, Gianluca Sbardella, Jean Cavarelli, Nathaniel I Martin
Coactivator associated arginine methyltransferase 1 (CARM1) is a member of the protein arginine methyltransferase (PRMT) family and methylates a range of proteins in eukaryotic cells. Overexpression of CARM1 is implicated in a number of cancers, and it is therefore seen as a potential therapeutic target. Peptide sequences derived from the well-defined CARM1 substrate poly(A)-binding protein 1 (PABP1) were covalently linked to an adenosine moiety as in the AdoMet cofactor to generate transition state mimics...
April 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28315332/nuclear-ampk-regulated-carm1-stabilization-impacts-autophagy-in-aged-heart
#5
Chen Li, Lu Yu, Han Xue, Zheng Yang, Yue Yin, Bo Zhang, Mai Chen, Heng Ma
Senescence-associated autophagy downregulation leads to cardiomyocyte dysfunction. Coactivator-associated arginine methyltransferase 1 (CARM1) participates in many cellular processes, including autophagy in mammals. However, the effect of CARM1 in aging-related cardiac autophagy decline remains undefined. Moreover, AMP-activated protein kinase (AMPK) is a key regulator in metabolism and autophagy, however, the role of nuclear AMPK in autophagy outcome in aged hearts still unclear. Hers we identify the correlation between nuclear AMPK and CARM1 in aging heart...
April 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28301308/regenerating-muscle-with-arginine-methylation
#6
Roméo S Blanc, Stéphane Richard
Protein arginine methyltransferase (PRMT) is a family of nine proteins catalyzing the methylation of arginine residues. They were recently shown to be essential for proper regeneration of skeletal muscles. However, the mechanisms triggering the methylation event, as well as how the methylated substrates regulate muscle stem cell function and fate decision remain to be determined. This point-of-view will discuss the recent findings on the specific role of PRMT1, CARM1/PRMT4, PRMT5, and PRMT7 in muscle stem cell fate guidance, and shed light on the future challenges which could help defining the therapeutic potential of PRMT inhibitors against muscular disorders and aging...
February 17, 2017: Transcription
https://www.readbyqxmd.com/read/28264928/inhibition-of-coactivator-associated-arginine-methyltransferase-1-modulates-dendritic-arborization-and-spine-maturation-of-cultured-hippocampal-neurons
#7
Chol Seung Lim, Daniel L Alkon
An improved understanding of the molecular mechanisms in synapse formation provides insight into both learning and memory and the etiology of neurodegenerative disorders. Coactivator-associated arginine methyltransferase 1 (CARM1) is a protein methyltransferase that negatively regulates synaptic gene expression and inhibits neuronal differentiation. Despite its regulatory function in neurons, little is known about the CARM1 cellular location and its role in dendritic maturation and synapse formation. Here, we examined the effects of CARM1 inhibition on dendritic spine and synapse morphology in the rat hippocampus...
April 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28255246/mir-195-enhances-the-radiosensitivity-of-colorectal-cancer-cells-by-suppressing-carm1
#8
Li Zheng, Jiangtao Chen, Zhongyong Zhou, Zhikuan He
BACKGROUND: microRNAs (miRNAs) can regulate the sensitivity of cancer cells to chemotherapy and radiotherapy. Aberrant expression of miR-195 has been found to be involved in colorectal cancer (CRC); however, its function and underlying mechanism in the radioresistance of CRC remains unclear. METHODS: The levels of miR-195 and CARM1 were detected by quantitative reverse transcription-polymerase chain reaction and Western blot analysis in HCT-116 and HT-29 cells, respectively...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28042453/design-and-synthesis-of-selective-small-molecule-inhibitors-of-coactivator-associated-arginine-methyltransferase-1-carm1
#9
H Ü Kaniskan, M S Eram, J Liu, D Smil, M L Martini, Y Shen, V Santhakumar, P J Brown, C Arrowsmith, M Vedadi, J Jin
Coactivator-associated arginine methyltransferase 1 (CARM1) is a type I protein arginine methyltransferase (PRMT) that catalyzes the conversion of arginine into monomethylarginine (MMA) and further into asymmetric dimethylarginine (ADMA). CARM1 methylates histone 3 arginines 17 and 26, as well as numerous non-histone proteins including CBP/p300, SRC-3, NCOA2, PABP1, and SAP49, while also functioning as a coactivator for various proteins that have been linked to cancer such as p53, NF-κβ, β-catenin, E2F1 and steroid hormone receptor ERα...
September 1, 2016: MedChemComm
https://www.readbyqxmd.com/read/27872854/identification-of-novel-inhibitors-against-coactivator-associated-arginine-methyltransferase-1-based-on-virtual-screening-and-biological-assays
#10
Fei Ye, Weiyao Zhang, Wenchao Lu, Yiqian Xie, Hao Jiang, Jia Jin, Cheng Luo
Overexpression of coactivator associated arginine methyltransferase 1 (CARM1), a protein arginine N-methyltransferase (PRMT) family enzyme, is associated with various diseases including cancers. Consequently, the development of small-molecule inhibitors targeting PRMTs has significant value for both research and therapeutic purposes. In this study, together with structure-based virtual screening with biochemical assays, two compounds DC_C11 and DC_C66 were identified as novel inhibitors of CARM1. Cellular studies revealed that the two inhibitors are cell membrane permeable and effectively blocked proliferation of cancer cells including HELA, K562, and MCF7...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27869171/epigenetic-activation-of-the-prostaglandin-receptor-ep4-promotes-resistance-to-endocrine-therapy-for-breast-cancer
#11
J F Hiken, J I McDonald, K F Decker, C Sanchez, J Hoog, N D VanderKraats, K L Jung, M Akinhanmi, L E Rois, M J Ellis, J R Edwards
Approximately 75% of breast cancers express estrogen receptor α (ERα) and depend on estrogen signals for continued growth. Aromatase inhibitors (AIs) prevent estrogen production and inhibit ER signaling, resulting in decreased cancer recurrence and mortality. Advanced tumors treated with AIs almost always develop resistance to these drugs via the upregulation of alternative growth signals. The mechanisms that drive this resistance-especially epigenetic events that alter gene expression-are, however, not well understood...
April 20, 2017: Oncogene
https://www.readbyqxmd.com/read/27867975/the-ampk-skp2-carm1-axis-links-nutrient-sensing-to-transcriptional-and-epigenetic-regulation-of-autophagy
#12
EDITORIAL
Ziheng Xu, Daniel J Klionsky
No abstract text is available yet for this article.
October 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/27680669/nucleolar-reorganization-upon-site-specific-double-strand-break-induction
#13
Michal Franek, Alena Kovaříková, Eva Bártová, Stanislav Kozubek
DNA damage response (DDR) in ribosomal genes and mechanisms of DNA repair in embryonic stem cells (ESCs) are less explored nuclear events. DDR in ESCs should be unique due to their high proliferation rate, expression of pluripotency factors, and specific chromatin signature. Given short population doubling time and fast progress through G1 phase, ESCs require a sustained production of rRNA, which leads to the formation of large and prominent nucleoli. Although transcription of rRNA in the nucleolus is relatively well understood, little is known about DDR in this nuclear compartment...
November 2016: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/27577262/proteome-wide-analysis-of-arginine-monomethylation-reveals-widespread-occurrence-in-human-cells
#14
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
https://www.readbyqxmd.com/read/27503676/arginine-di-methylated-human-leukocyte-antigen-class-i-peptides-are-favorably-presented-by-hla-b-07
#15
Fabio Marino, Geert P M Mommen, Anita Jeko, Hugo D Meiring, Jacqueline A M van Gaans-van den Brink, Richard A Scheltema, Cécile A C M van Els, Albert J R Heck
Alterations in protein post-translational modification (PTM) 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 dimethylated arginine residues by mass spectrometry...
January 6, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/27487449/epigenetic-and-transcriptional-regulation-of-autophagy
#16
Hi-Jai R Shin, Hyunkyung Kim, Keun Il Kim, Sung Hee Baek
Macroautophagy (hereafter referred to as autophagy) is an essential self-digestion process to maintain homeostasis and promote survival in response to starvation. Although the components of autophagy in the cytoplasm have been well studied, little has been known about the fine-tuning mechanism of autophagy through epigenetic regulations. Recently, we identified the histone arginine methyltransferase CARM1 as a new component and followed histone H3R17 dimethylation as a critical epigenetic mark in starvation-induced autophagy...
November 2016: Autophagy
https://www.readbyqxmd.com/read/27486787/correction-to-discovery-of-a-potent-and-selective-coactivator-associated-arginine-methyltransferase-1-carm1-inhibitor-by-virtual-screening
#17
Renato Ferreira de Freitas, Mohammad S Eram, David Smil, Magdalena M Szewczyk, Steven Kennedy, Peter J Brown, Vijayaratnam Santhakumar, Dalia Barsyte-Lovejoy, Cheryl H Arrowsmith, Masoud Vedadi, Matthieu Schapira
No abstract text is available yet for this article.
August 25, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27479032/carm1-methylates-chromatin-remodeling-factor-baf155-to-enhance-tumor-progression-and-metastasis
#18
Lu Wang, Zibo Zhao, Mark B Meyer, Sandeep Saha, Menggang Yu, Ailan Guo, Kari B Wisinski, Wei Huang, Weibo Cai, J Wesley Pike, Ming Yuan, Paul Ahlquist, Wei Xu
No abstract text is available yet for this article.
July 11, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27390919/discovery-of-a-potent-and-selective-coactivator-associated-arginine-methyltransferase-1-carm1-inhibitor-by-virtual-screening
#19
Renato Ferreira de Freitas, Mohammad S Eram, David Smil, Magdalena M Szewczyk, Steven Kennedy, Peter J Brown, Vijayaratnam Santhakumar, Dalia Barsyte-Lovejoy, Cheryl H Arrowsmith, Masoud Vedadi, Matthieu Schapira
Protein arginine methyltransferases (PRMTs) represent an emerging target class in oncology and other disease areas. So far, the most successful strategy to identify PRMT inhibitors has been to screen large to medium-size chemical libraries. Attempts to develop PRMT inhibitors using receptor-based computational methods have met limited success. Here, using virtual screening approaches, we identify 11 CARM1 (PRMT4) inhibitors with ligand efficiencies ranging from 0.28 to 0.84. CARM1 selective hits were further validated by orthogonal methods...
July 28, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27338245/using-oriented-peptide-array-libraries-to-evaluate-methylarginine-specific-antibodies-and-arginine-methyltransferase-substrate-motifs
#20
Sitaram Gayatri, Martis W Cowles, Vidyasiri Vemulapalli, Donghang Cheng, Zu-Wen Sun, Mark T Bedford
Signal transduction in response to stimuli relies on the generation of cascades of posttranslational modifications that promote protein-protein interactions and facilitate the assembly of distinct signaling complexes. Arginine methylation is one such modification, which is catalyzed by a family of nine protein arginine methyltransferases, or PRMTs. Elucidating the substrate specificity of each PRMT will promote a better understanding of which signaling networks these enzymes contribute to. Although many PRMT substrates have been identified, and their methylation sites mapped, the optimal target motif for each of the nine PRMTs has not been systematically addressed...
2016: Scientific Reports
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