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histone ubiquitination

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https://www.readbyqxmd.com/read/28534629/synthetic-posttranslational-modifications-chemical-catalyst-driven-regioselective-histone-acylation-of-native-chromatin
#1
Yoshifumi Amamoto, Yuki Aoi, Nozomu Nagashima, Hiroki Suto, Daisuke Yoshidome, Yasuhiro Arimura, Akihisa Osakabe, Daiki Kato, Hitoshi Kurumizaka, Shigehiro A Kawashima, Kenzo Yamatsugu, Motomu Kanai
Posttranslational modifications (PTMs) of histones play an important role in the complex regulatory mechanisms governing gene transcription, and their dysregulation can cause diseases such as cancer. The lack of methods for site-selectively modifying native chromatin, however, limits our understanding of the functional roles of a specific histone PTM, not as a single mark, but in the intertwined PTM network. Here, we report a synthetic catalyst DMAP-SH (DSH), which activates chemically stable thioesters (including acetyl-CoA) under physiological conditions and transfers various acyl groups to the proximate amino groups...
May 23, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28534506/lsd1-demethylates-hif1%C3%AE-to-inhibit-hydroxylation-and-ubiquitin-mediated-degradation-in-tumor-angiogenesis
#2
J-Y Lee, J-H Park, H-J Choi, H-Y Won, H-S Joo, D-H Shin, M K Park, B Han, K P Kim, T J Lee, C M Croce, G Kong
Lysine-specific demethylase 1 (LSD1), which has been considered as a potential therapeutic target in human cancer, has been known to regulate many biological functions through its non-histone substrates. Although LSD1-induced hypoxia-inducible factor alpha (HIF1α) demethylation has recently been proposed, the effect of LSD1 on the relationship between HIF1α post-translational modifications (PTMs) and HIF1α-induced tumor angiogenesis remains to be elucidated. Here, we identify a new methylation site of the HIF1α protein antagonized by LSD1 and the interplay between HIF1α protein methylation and other PTMs in regulating tumor angiogenesis...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28532323/quantitative-regulation-of-histone-variant-h2a-z-during-cell-cycle-by-ubiquitin-proteasome-system-and-sumo-targeted-ubiquitin-ligases
#3
Daisuke Takahashi, Yuki Orihara, Saho Kitagawa, Masayuki Kusakabe, Takahiro Shintani, Yukako Oma, Masahiko Harata
Quantitative control of histones and histone variants during cell cycle is relevant to their epigenetic functions. We found that the level of yeast histone variant H2A.Z in the G2/M-phase is actively kept low by the ubiquitin proteasome system and SUMO-targeted ubiquitin ligases. Overexpression of H2A.Z induced defects in mitotic progression, suggesting functional importance of this quantitative control.
May 22, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28525742/ubiquitin-modification-by-the-e3-ligase-adp-ribosyltransferase-dtx3l-parp9
#4
Chun-Song Yang, Kasey Jividen, Adam Spencer, Natalia Dworak, Li Ni, Luke T Oostdyk, Mandovi Chatterjee, Beata Kuśmider, Brian Reon, Mahmut Parlak, Vera Gorbunova, Tarek Abbas, Erin Jeffery, Nicholas E Sherman, Bryce M Paschal
ADP-ribosylation of proteins is emerging as an important regulatory mechanism. Depending on the family member, ADP-ribosyltransferases either conjugate a single ADP-ribose to a target or generate ADP-ribose chains. Here we characterize Parp9, a mono-ADP-ribosyltransferase reported to be enzymatically inactive. Parp9 undergoes heterodimerization with Dtx3L, a histone E3 ligase involved in DNA damage repair. We show that the Dtx3L/Parp9 heterodimer mediates NAD(+)-dependent mono-ADP-ribosylation of ubiquitin, exclusively in the context of ubiquitin processing by E1 and E2 enzymes...
May 18, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28525740/rnf8-and-ube2s-dependent-ubiquitin-lysine-11-linkage-modification-in-response-to-dna-damage
#5
Atanu Paul, Bin Wang
Ubiquitin modification of proteins plays pivotal roles in the cellular response to DNA damage. Given the complexity of ubiquitin conjugation due to the formation of poly-conjugates of different linkages, functional roles of linkage-specific ubiquitin modification at DNA damage sites are largely unclear. We identify that Lys11-linkage ubiquitin modification occurs at DNA damage sites in an ATM-dependent manner, and ubiquitin-modifying enzymes, including Ube2S E2-conjugating enzyme and RNF8 E3 ligase, are responsible for the assembly of Lys11-linkage conjugates on damaged chromatin, including histone H2A/H2AX...
May 18, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28506460/mechanisms-of-ubiquitin-nucleosome-recognition-and-regulation-of-53bp1-chromatin-recruitment-by-rnf168-169-and-rad18
#6
Qi Hu, Maria Victoria Botuyan, Gaofeng Cui, Debiao Zhao, Georges Mer
The protein 53BP1 plays a central regulatory role in DNA double-strand break repair. 53BP1 relocates to chromatin by recognizing RNF168-mediated mono-ubiquitylation of histone H2A Lys15 in the nucleosome core particle dimethylated at histone H4 Lys20 (NCP-ubme). 53BP1 relocation is terminated by ubiquitin ligases RNF169 and RAD18 via unknown mechanisms. Using nuclear magnetic resonance (NMR) spectroscopy and biochemistry, we show that RNF169 bridges ubiquitin and histone surfaces, stabilizing a pre-existing ubiquitin orientation in NCP-ubme to form a high-affinity complex...
May 18, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28505447/interrogating-the-roles-of-post-translational-modifications-of-non-histone-proteins
#7
Zakey Yusuf Buuh, Zhigang Lyu, Rongsheng E Wang
Post-translational modifications (PTMs) allot versatility to the biological functions of highly conserved proteins. Recently, modifications to non-histone proteins such as methylation, acetylation, phosphorylation, glycosylation, ubiquitination, and many more have been linked to the regulation of pivotal pathways related to cellular response and stability. Due to the roles these dynamic modifications assume, their dysregulation has been associated with cancer and many other important diseases such as inflammatory disorders and neurodegenerative diseases...
May 15, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28501850/the-epigenetic-integrator-uhrf1-on-the-road-to-become-a-universal-biomarker-for-cancer
#8
REVIEW
Waseem Ashraf, Abdulkhaleg Ibrahim, Mahmoud Alhosin, Liliyana Zaayter, Khalid Ouararhni, Christophe Papin, Tanveer Ahmad, Ali Hamiche, Yves Mély, Christian Bronner, Marc Mousli
Cancer is one of the deadliest diseases in the world causing record number of mortalities in both developed and undeveloped countries. Despite a lot of advances and breakthroughs in the field of oncology still, it is very hard to diagnose and treat the cancers at early stages. Here in this review we analyze the potential of Ubiquitin-like containing PHD and Ring Finger domain 1 (UHRF1) as a universal biomarker for cancers. UHRF1 is an important epigenetic regulator maintaining DNA methylation and histone code in the cell...
April 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28484595/fetal-and-neonatal-programming-of-postnatal-growth-and-feed-efficiency-in-swine
#9
REVIEW
Yun Ji, Zhenlong Wu, Zhaolai Dai, Xiaolong Wang, Ju Li, Binggen Wang, Guoyao Wu
Maternal undernutrition or overnutrition during pregnancy alters organ structure, impairs prenatal and neonatal growth and development, and reduces feed efficiency for lean tissue gains in pigs. These adverse effects may be carried over to the next generation or beyond. This phenomenon of the transgenerational impacts is known as fetal programming, which is mediated by stable and heritable alterations of gene expression through covalent modifications of DNA and histones without changes in DNA sequences (namely, epigenetics)...
2017: Journal of Animal Science and Biotechnology
https://www.readbyqxmd.com/read/28483947/regulation-of-usp37-expression-by-rest-associated-g9a-dependent-histone-methylation
#10
Tara Dobson, Rashieda J Hatcher, Jyothismathi Swaminathan, Chandra M Das, Shavali Shaik, Rong-Hua Tao, Ciro Milite, Sabrina Castellano, Pete Taylor, Gianluca Sbardella, Vidya Gopalakrishnan
The deubiquitylase (DUB) USP37 is a component of the ubiquitin system and controls cell proliferation by regulating the stability of the cyclin-dependent kinase inhibitor 1B, (CDKN1B/p27Kip1). The expression of USP37 is down-regulated in human medulloblastoma tumor specimens. In the current study we show that USP37 prevents medulloblastoma growth in mouse orthotopic models, suggesting that it has tumor suppressive properties in this neural cancer. Here, we also report on the mechanism underlying USP37 loss in medulloblastoma...
May 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28481029/loss-of-h2b-monoubiquitination-is-associated-with-poor-differentiation-and-enhanced-malignancy-of-lung-adenocarcinoma
#11
Keqiang Zhang, Jinhui Wang, Tommy R Tong, Xiwei Wu, Rebecca Nelson, Yate-Ching Yuan, Theresa Reno, Zheng Liu, Xinwei Yun, Jae Y Kim, Ravi Salgia, Dan J Raz
Deregulated monoubiquitination of histone H2B (H2Bub1), mainly catalyzed by E3 ubiquitin-protein ligase RNF20/RNF40 complex, may play an important role in cancer. Here we investigate potential roles of H2Bub1 and the underlying mechanisms through which it contributes to cancer development and progression in lung adenocarcinoma. We show that downregulation of H2Bub1 through RNF20 knockdown dramatically decreases H3K79 and H3K4 trimethylation in both normal and malignant lung epithelial cell lines. Concurrently, global transcriptional profiling analysis reveals that multiple tumor-associated genes such as CCND3, E2F1/2, HOXA1, Bcl2 modifying factor (BMF), Met, and Myc; and signaling pathways of cellular dedifferentiation, proliferation, adhesion, survival including p53, cadherin, Myc, and anti-apoptotic pathways are differentially expressed or significantly altered in these lung epithelial cells upon downregulation of H2Bub1...
May 8, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28474855/chromatin-regulates-genome-targeting-with-cisplatin
#12
Emmanouil Zacharioudakis, Poonam Agarwal, Alexandra Bartoli, Nathan Abell, Lavaniya Kunalingam, Valérie Bergoglio, Blerta Xhemalce, Kyle M Miller, Raphaël Rodriguez
Cisplatin derivatives can form various types of DNA lesions (DNA-Pt) and trigger pleiotropic DNA damage responses. Here, we report a strategy to visualize DNA-Pt with high resolution, taking advantage of a novel azide-containing derivative of cisplatin we named APPA, a cellular pre-extraction protocol and the labeling of DNA-Pt by means of click chemistry in cells. Our investigation revealed that pretreating cells with the histone deacetylase (HDAC) inhibitor SAHA led to detectable clusters of DNA-Pt that colocalized with the ubiquitin ligase RAD18 and the replication protein PCNA...
June 1, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28472782/identification-of-deubiquitinase-targets-of-isothiocyanates-using-silac-assisted-quantitative-mass-spectrometry
#13
Ann P Lawson, Daniel W Bak, D Alexander Shannon, Marcus J C Long, Tushara Vijaykumar, Runhan Yu, Farid El Oualid, Eranthie Weerapana, Lizbeth Hedstrom
Cruciferous vegetables such as broccoli and kale have well documented chemopreventative and anticancer effects that are attributed to the presence of isothiocyanates (ITCs). ITCs modulate the levels of many oncogenic proteins, but the molecular mechanisms of ITC action are not understood. We previously reported that phenethyl isothiocyanate (PEITC) inhibits two deubiquitinases (DUBs), USP9x and UCH37. DUBs regulate many cellular processes and DUB dysregulation is linked to the pathogenesis of human diseases including cancer, neurodegeneration, and inflammation...
April 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28464229/functional-characterization-of-the-neuron-restrictive-silencer-element-in-the-human-tryptophan-hydroxylase-2-gene-expression
#14
Yukino Nawa, Hanae Kaneko, Masayuki Oda, Masaaki Tsubonoya, Tomoko Hiroi, Maria Teresa Gentile, Luca Colucci-D'Amato, Ryoya Takahashi, Hiroaki Matsui
Tryptophan hydroxylase 2 (TPH2) is the key enzyme in the synthesis of neuronal serotonin. Although previous studies suggest that TPH2 NRSE (neuron-restrictive silencer element) functions as a negative regulator dependent on NRSF (neuron-restrictive silencer factor) activity, the underlying mechanisms are yet to be fully elucidated. Here, we show a detailed analysis of the NRSE-mediated repression of the human TPH2 (hTPH2) promoter activity in RN46A cells, a cell line derived from rat raphe neurons. Quantitative real-time RT-PCR analysis revealed the expression of serotonergic marker genes (Mash1, Nkx2...
May 2, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28453857/fbxl19-recruitment-to-cpg-islands-is-required-for-rnf20-mediated-h2b-mono-ubiquitination
#15
Bum-Kyu Lee, Jiwoon Lee, Wenwen Shen, Catherine Rhee, Haewon Chung, Jonghwan Kim
Histone H2B lysine 120 mono-ubiquitination (H2Bub1) catalyzed by Rnf20 has been implicated in normal differentiation of embryonic stem (ES) and adult stem cells. However, it remains unknown how Rnf20 is recruited to its specific target chromosomal loci for the establishment of H2Bub1. Here, we reveal that Fbxl19, a CxxC domain-containing protein, promotes H2Bub1 at the promoters of CpG island-containing genes by interacting with Rnf20. We show that up-regulation of Fbxl19 increases the level of global H2Bub1 in mouse ES cells, while down-regulation of Fbxl19 reduces the level of H2Bub1...
April 27, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28450160/a-novel-histone-deacetylase-inhibitor-tmu-35435-enhances-etoposide-cytotoxicity-through-the-proteasomal-degradation-of-dna-pkcs-in-triple-negative-breast-cancer
#16
Yuan-Hua Wu, Chi-Wei Hong, Yi-Ching Wang, Wei-Jan Huang, Ya-Ling Yeh, Bour-Jr Wang, Ying-Jan Wang, Hui-Wen Chiu
Triple-negative breast cancer (TNBC) treatment offers only limited benefits, and it is very relevant given the significant number of deaths that it causes. DNA repair pathways can enable tumor cells to survive DNA damage that is induced by chemotherapeutic or radiation treatments. Histone deacetylase inhibitors (HDACi) inhibited DNA repair proteins. However, the detailed mechanisms for this inhibition remain unclear. In the present study, we investigated whether a newly developed HDACi, TMU-35435, could enhance etoposide cytotoxicity by inhibiting DNA repair proteins in triple-negative breast cancer...
April 25, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28445968/usp22-knockdown-enhanced-chemosensitivity-of-hepatocellular-carcinoma-cells-to-5-fu-by-up-regulation-of-smad4-and-suppression-of-akt
#17
Jing Zhang, Nan Luo, Yu Tian, Jiazhi Li, Xiaozhou Yang, Huimin Yin, Congshu Xiao, Jie Sheng, Yang Li, Bo Tang, Rongkuan Li
USP22, a member of the deubiquitinases (DUBs) family, is known to be a key subunit of the human Spt-Ada-Gcn5 acetyltransferase (hSAGA) transcriptional cofactor complex. Within hSAGA, USP22 removes ubiquitin from histone proteins, thus regulating the transcription and expression of downstream genes. USP22 plays important roles in many cancers; however, its effect and the mechanism underlying HCC chemoresistance remain unclear. In the present study, we found that USP22 was highly expressed in chemoresistant HCC tissues and cells and was correlated with the prognosis of HCC patients who received chemotherapy...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28433423/prefrontal-cortex-expression-of-chromatin-modifier-genes-in-male-wsp-and-wsr-mice-changes-across-ethanol-dependence-withdrawal-and-abstinence
#18
Joel G Hashimoto, David P Gavin, Kristine M Wiren, John C Crabbe, Marina Guizzetti
Alcohol-use disorder (AUD) is a relapsing disorder associated with excessive ethanol consumption. Recent studies support the involvement of epigenetic mechanisms in the development of AUD. Studies carried out so far have focused on a few specific epigenetic modifications. The goal of this project was to investigate gene expression changes of epigenetic regulators that mediate a broad array of chromatin modifications after chronic alcohol exposure, chronic alcohol exposure followed by 8 h withdrawal, and chronic alcohol exposure followed by 21 days of abstinence in Withdrawal-Resistant (WSR) and Withdrawal Seizure-Prone (WSP) selected mouse lines...
May 2017: Alcohol
https://www.readbyqxmd.com/read/28423597/hrd1-sensitizes-breast-cancer-cells-to-tamoxifen-by-promoting-s100a8-degradation
#19
YanYang Wang, AiBin Guo, XiuBin Liang, Min Li, Ming Shi, Yan Li, Gareth Jenkins, XiaWen Lin, XueFei Wei, ZhiJun Jia, XueFeng Feng, DongMing Su, WanHua Guo
Estrogen receptor alpha positive (ER+) of breast cancer could develop resistance to antiestrogens including Tamoxifen. Our previous study showed that the E3 ubiquitin ligase HRD1 played an important role in anti-breast cancer. However, its role in chemotherapy resistance hasn't been reported. In this study, we found that HRD1 expression was downregulated in Tamoxifen-resistant breast cancer cell line MCF7/Tam compared to the Tamoxifen sensitive cell line MCF7. Moreover, S100A8 is the direct target of HRD1 by proteome analysis...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416769/nuclear-organization-of-nucleotide-excision-repair-is-mediated-by-ring1b-dependent-h2a-ubiquitylation
#20
Shalaka Chitale, Holger Richly
One of the major cellular DNA repair pathways is nucleotide excision repair (NER). It is the primary pathway for repair of various DNA lesions caused by exposure to ultraviolet (UV) light, such as cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts. Although lesion-containing DNA associates with the nuclear matrix after UV irradiation it is still not understood how nuclear organization affects NER. Analyzing unscheduled DNA synthesis (UDS) indicates that NER preferentially occurs in specific nuclear areas, viz the nucleolus...
May 9, 2017: Oncotarget
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