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UHRF1

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https://www.readbyqxmd.com/read/29656054/biochemical-and-dynamic-basis-for-combinatorial-recognition-of-h3r2k9me2-by-dual-domains-of-uhrf1
#1
Suman Abhishek, M Angel Nivya, Naveen Kumar Nakarakanti, Waghela Deeksha, Sanjeev Khosla, Eerappa Rajakumara
UHRF1 is a multi-domain protein comprising of a tandem tudor (UHRF1 TTD), a PHD finger, and a SET and RING-associated domain. It is required for the maintenance of CG methylation, heterochromatin formation and DNA repair. Isothermal titration calorimetry binding studies of unmodified and methylated lysine histone peptides establish that the UHRF1 TTD binds dimethylated Lys9 on histone H3 (H3K9me2). Further, MD simulation and binding studies reveal that TTD-PHD of UHRF1 (UHRF1 TTD-PHD) preferentially recognizes dimethyl-lysine status...
April 12, 2018: Biochimie
https://www.readbyqxmd.com/read/29620240/upregulation-of-uhrf1-promotes-the-progression-of-melanoma-by-inducing-cell-proliferation
#2
Chuanyuan Wei, Nanhang Lu, Lu Wang, Yong Zhang, Zihao Feng, Yanwen Yang, Fazhi Qi, Jianying Gu
Melanoma is the most aggressive cutaneous cancer due to its propensity to metastasise and proliferate. Melanoma accounts for 80‑90% of skin‑cancer related deaths worldwide. Alhough numerous published studies have attempted to define the markers of diagnosis and prognosis of melanoma, a sensitive and specific biomarker for melanoma remains unknown. Recently, ubiquitin‑like with PHD and ring finger domains 1 (UHRF1) has attracted attention due to its role in cell proliferation and it has been deemed as a potential therapeutic target for cancer...
April 4, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29618490/uhrf1-regulates-germinal-center-b-cell-expansion-and-affinity-maturation-to-control-viral-infection
#3
Chao Chen, Sulan Zhai, Le Zhang, Jingjing Chen, Xuehui Long, Jun Qin, Jianhua Li, Ran Huo, Xiaoming Wang
The production of high-affinity antibody is essential for pathogen clearance. Antibody affinity is increased through germinal center (GC) affinity maturation, which relies on BCR somatic hypermutation (SHM) followed by antigen-based selection. GC B cell proliferation is essentially involved in these processes; it provides enough templates for SHM and also serves as a critical mechanism of positive selection. In this study, we show that expression of epigenetic regulator ubiquitin-like with PHD and RING finger domains 1 (Uhrf1) was markedly up-regulated by c-Myc-AP4 in GC B cells, and it was required for GC response...
April 4, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29616129/line-1-hypomethylation-is-inversely-correlated-with-uhrf1-overexpression-in-gastric-cancer
#4
Jang Hee Hong, Eun-Heui Jin, Soyeon Kim, Kyu-Sang Song, Jae Kyu Sung
DNA methylation is an important epigenetic modification that alters gene expression; DNA hypomethylation contributes to tumorigenesis through multiple processes. In the present study, the methylation of long interspersed element-1 (LINE-1) in 95 gastric cancer (GC) tissues and matched adjacent normal tissues was investigated by pyrosequencing. LINE-1 methylation was compared with the expression of ubiquitin-like with PHD and ring-finger protein 1 (UHRF1), an essential regulator of DNA methylation, using reverse transcription-quantitative polymerase chain reaction...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29572246/comparative-proteomics-of-dying-and-surviving-cancer-cells-improves-the-identification-of-drug-targets-and-sheds-light-on-cell-life-death-decisions
#5
Amir Ata Saei, Pierre Sabatier, Ülkü Güler Tokat, Alexey Chernobrovkin, Mohammad Pirmoradian, Roman A Zubarev
Chemotherapeutics cause the detachment and death of adherent cancer cells. When studying the proteome changes to determine the protein target and mechanism of action of anticancer drugs, the still-attached cells are normally used, while the detached cells are usually ignored. To test the hypothesis that proteomes of detached cells contain valuable information, we separately analyzed the proteomes of detached and attached HCT-116, A375 and RKO cells treated for 48 h with 5-fluorouracil, methotrexate and paclitaxel...
March 23, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29562800/discovery-of-small-molecule-antagonists-of-the-h3k9me3-binding-to-uhrf1-tandem-tudor-domain
#6
Guillermo Senisterra, Hugh Y Zhu, Xiao Luo, Hailong Zhang, Guoliang Xun, Chunliang Lu, Wen Xiao, Taraneh Hajian, Peter Loppnau, Irene Chau, Fengling Li, Abdellah Allali-Hassani, Peter Atadja, Counde Oyang, En Li, Peter J Brown, Cheryl H Arrowsmith, Kehao Zhao, Zhengtian Yu, Masoud Vedadi
Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) is a multidomain protein that plays a critical role in maintaining DNA methylation patterns through concurrent recognition of hemimethylated DNA and histone marks by various domains, and recruitment of DNA methyltransferase 1 (DNMT1). UHRF1 is overexpressed in various cancers, including breast cancer. The tandem tudor domain (TTD) of UHRF1 specifically and tightly binds to histone H3 di- or trimethylated at lysine 9 (H3K9me2 or H3K9me3, respectively), and this binding is essential for UHRF1 function...
March 1, 2018: SLAS Discovery
https://www.readbyqxmd.com/read/29558369/uhrf1-epigenetically-orchestrates-smooth-muscle-cell-plasticity-in-arterial-disease
#7
Leonardo Elia, Paolo Kunderfranco, Pierluigi Carullo, Marco Vacchiano, Floriana Maria Farina, Ignacio Fernando Hall, Stefano Mantero, Cristina Panico, Roberto Papait, Gianluigi Condorelli, Manuela Quintavalle
Adult vascular smooth muscle cells (VSMCs) possess the peculiar ability to de-differentiate in response to extracellular cues, such as vascular damage and inflammation. De-differentiated VSMCs are proliferative, migratory, and have decreased contractile capacity. VSMC dedifferentiation contributes not only to vascular repair, but also to cardiovascular pathologies, such as intimal hyperplasia/restenosis in coronary artery or peripheral vascular diseases and arterial aneurysm. We here demonstrate the role of ubiquitin-like, containing PHD and RING finger domains, 1 (UHRF1) as an epigenetic master regulator of VSMC plasticity...
March 20, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29525533/maternal-green-tea-polyphenol-intake-during-lactation-attenuates-kidney-injury-in-high-fat-diet-fed-male-offspring-programmed-by-maternal-protein-restriction-in-rats
#8
Saori Kataoka, Toshio Norikura, Shin Sato
Maternal malnutrition is known to increase the risk of obesity in offspring. We investigated whether green tea extract (GTE) intake during lactation affects obesity-related fibrosis and inflammation in the kidney of high-fat-diet-fed adult offspring of protein-restricted-diet-fed dams during pregnancy and lactation. Pregnant Wistar rats received diets containing 20% (normal-protein, NP) or 8% (low-protein, LP) casein, and they received 0%-, 0.12%- or 0.24%-GTE-containing LP diets (LP/LP, LP/LGT and LP/HGT, respectively) during lactation...
February 9, 2018: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29516630/wdr79-mediates-the-proliferation-of-non-small-cell-lung-cancer-cells-by-regulating-the-stability-of-uhrf1
#9
Jieying Chen, Xunan Sheng, Hongchang Ma, Zhengshan Tang, Chao Yang, Lanqin Cao, Yang Sun, Tanggang Deng, Peifu Feng, Bin Hu, Dong Wei, Jing Liu, Wei Xiong, Mao Ye
WD repeat protein 79 (WDR79) is a member of the WD-repeat protein family characterized by the presence of a series of WD-repeat domains and is a scaffold protein that participates in telomerase assembly, Cajal body formation and DNA double strand break repair. Although previous studies have revealed that WDR79 is frequently overexpressed in non-small cell lung cancer (NSCLC) and promotes the proliferation of NSCLC cells, the underlying mechanism responsible for WDR79-mediated NSCLC proliferation is not fully understood...
March 7, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29507645/overexpression-of-uhrf1-promotes-silencing-of-tumor-suppressor-genes-and-predicts-outcome-in-hepatoblastoma
#10
Alexander Beck, Franziska Trippel, Alexandra Wagner, Saskia Joppien, Max Felle, Christian Vokuhl, Thomas Schwarzmayr, Tim M Strom, Dietrich von Schweinitz, Gernot Längst, Roland Kappler
Background: Hepatoblastoma (HB) is the most common liver tumor of childhood and occurs predominantly within the first 3 years of life. In accordance to its early manifestation, HB has been described to display an extremely low mutation rate. As substitute, epigenetic modifiers seem to play an exceptional role in its tumorigenesis, which holds promise to develop targeted therapies and establish biomarkers for patient risk stratification. Results: We examined the role of a newly described protein complex consisting of three epigenetic regulators, namely E3 ubiquitin-like containing PHD and RING finger domain 1 (UHRF1), ubiquitin-specific-processing protease 7 (USP7), and DNA methyltransferase 1 (DNMT1), in HB...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29506131/comparative-biochemical-analysis-of-uhrf-proteins-reveals-molecular-mechanisms-that-uncouple-uhrf2-from-dna-methylation-maintenance
#11
Robert M Vaughan, Bradley M Dickson, Evan M Cornett, Joseph S Harrison, Brian Kuhlman, Scott B Rothbart
UHRF1 is a histone- and DNA-binding E3 ubiquitin ligase that functions with DNMT1 to maintain mammalian DNA methylation. UHRF1 facilitates DNMT1 recruitment to replicating chromatin through a coordinated mechanism involving histone and DNA recognition and histone ubiquitination. UHRF2 shares structural homology with UHRF1, but surprisingly lacks functional redundancy to facilitate DNA methylation maintenance. Molecular mechanisms uncoupling UHRF2 from DNA methylation maintenance are poorly defined. Through comprehensive and comparative biochemical analysis of recombinant human UHRF1 and UHRF2 reader and writer activities, we reveal conserved modes of histone PTM recognition but divergent DNA binding properties...
February 28, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29471350/structural-and-mechanistic-insights-into-uhrf1-mediated-dnmt1-activation-in-the-maintenance-dna-methylation
#12
Tao Li, Linsheng Wang, Yongming Du, Si Xie, Xi Yang, Fuming Lian, Zhongjun Zhou, Chengmin Qian
UHRF1 plays multiple roles in regulating DNMT1-mediated DNA methylation maintenance during DNA replication. The UHRF1 C-terminal RING finger functions as an ubiquitin E3 ligase to establish histone H3 ubiquitination at Lys18 and/or Lys23, which is subsequently recognized by DNMT1 to promote its localization onto replication foci. Here, we present the crystal structure of DNMT1 RFTS domain in complex with ubiquitin and highlight a unique ubiquitin binding mode for the RFTS domain. We provide evidence that UHRF1 N-terminal ubiquitin-like domain (UBL) also binds directly to DNMT1...
February 19, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29466696/uhrf1-regulates-cdh1-via-promoter-associated-non-coding-rnas-in-prostate-cancer-cells
#13
Elena Magnani, Filippo Macchi, Monica Mancini, Vanessa Lomazzi, Sara Cogliati, Christian Pistore, Martina Mandruzzato, Anne-Catherine Dock-Bregeon, Ian Marc Bonapace
Non-coding RNAs (ncRNAs) transcribed from the promoter and the downstream region can affect the expression of the corresponding coding genes. It has been shown that sense-directed ncRNAs arising from the promoter region of the E-cadherin gene (CDH1) mediate its repression. Here, we show that an antisense-directed ncRNA (paRCDH1-AS) transcribed from the CDH1 promoter is necessary for its expression. paRCDH1-AS acts as a hooking scaffold by recruiting the epigenetic regulators, UHRF1, DNMT3A, SUV39H1 and SUZ12, involved in CDH1 repression...
February 18, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29449903/specific-or-not-specific-recruitment-of-dnmts-for-dna-methylation-an-epigenetic-dilemma
#14
REVIEW
Eric Hervouet, Paul Peixoto, Régis Delage-Mourroux, Michaël Boyer-Guittaut, Pierre-François Cartron
Our current view of DNA methylation processes is strongly moving: First, even if it was generally admitted that DNMT3A and DNMT3B are associated with de novo methylation and DNMT1 is associated with inheritance DNA methylation, these distinctions are now not so clear. Secondly, since one decade, many partners of DNMTs have been involved in both the regulation of DNA methylation activity and DNMT recruitment on DNA. The high diversity of interactions and the combination of these interactions let us to subclass the different DNMT-including complexes...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29415984/uhrf1-depletion-sensitizes-retinoblastoma-cells-to-chemotherapeutic-drugs-via-downregulation-of-xrcc4
#15
Heng He, Chunsik Lee, Jong Kyong Kim
UHRF1 (ubiquitin-like with PHD and ring finger domains 1) is highly expressed in various human cancers including retinoblastoma, and associated with tumor-promoting effects such as inhibition of apoptosis and high proliferation. However, the molecular mechanisms underlying tumor-promoting functions of UHRF1 in retinoblastoma still remain elusive. Here, we show that stable knockdown of UHRF1 renders retinoblastoma cells sensitized to conventional chemotherapeutic drugs such as etoposide and camptothecin, resulting in enhanced DNA damage and apoptotic cell death...
February 7, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29395786/an-intramolecular-interaction-of-uhrf1-reveals-dual-control-for-its-histone-association
#16
Linfeng Gao, Xiao-Feng Tan, Shen Zhang, Tianchen Wu, Zhi-Min Zhang, Hui-Wang Ai, Jikui Song
UHRF1 (ubiquitin-like, containing PHD and RING finger domains, 1) is one of the essential components of mammalian DNA methylation machinery. Chromatin association of UHRF1 is controlled via an interplay between its intramolecular interaction and dual recognition of histone H3 trimethylated at lysine 9 (H3K9me3) and hemimethylated DNA. Here, we report the crystal structure of the N-terminal tandem Tudor domain (TTD) of UHRF1 in complex with the C-terminal polybasic region (PBR). Structural analysis reveals that PBR binding leads to displacement of the TTD-plant homeodomain (PHD) linker, as well as blockage of the H3K9me3-engaging cage, both of which contribute to a chromatin-occluded UHRF1 conformation...
January 18, 2018: Structure
https://www.readbyqxmd.com/read/29285183/targeting-microrna-uhrf1-pathways-as-a-novel-strategy-for-cancer-therapy
#17
Hani Choudhry, Mazin A Zamzami, Ziad Omran, Wei Wu, Marc Mousli, Christian Bronner, Mahmoud Alhosin
Ubiquitin-like containing plant homeodomain and RING finger domains 1 (UHRF1) is an anti-apoptotic protein involved in the silencing of several tumor suppressor genes (TSGs) through epigenetic modifications including DNA methylation and histone post-translational alterations, and also epigenetic-independent mechanisms. UHRF1 overexpression is observed in a number of solid tumors and hematological malignancies, and is considered a primary mechanism in inhibiting apoptosis. UHRF1 exerts its inhibitory activity on TSGs by binding to functional domains and therefore influences several epigenetic actors including DNA methyltransferase, histone deacetylase 1, histone acetyltransferase Tat-interacting protein 60 and histone methyltransferases G9a and Suv39H1...
January 2018: Oncology Letters
https://www.readbyqxmd.com/read/29262320/the-arginine-methyltransferase-prmt6-regulates-dna-methylation-and-contributes-to-global-dna-hypomethylation-in-cancer
#18
Nicolas Veland, Swanand Hardikar, Yi Zhong, Sitaram Gayatri, Jiameng Dan, Brian D Strahl, Scott B Rothbart, Mark T Bedford, Taiping Chen
DNA methylation plays crucial roles in chromatin structure and gene expression. Aberrant DNA methylation patterns, including global hypomethylation and regional hypermethylation, are associated with cancer and implicated in oncogenic events. How DNA methylation is regulated in developmental and cellular processes and dysregulated in cancer is poorly understood. Here, we show that PRMT6, a protein arginine methyltransferase responsible for asymmetric dimethylation of histone H3 arginine 2 (H3R2me2a), negatively regulates DNA methylation and that PRMT6 upregulation contributes to global DNA hypomethylation in cancer...
December 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/29234018/dynamics-of-rif1-sumoylation-is-regulated-by-pias4-in-the-maintenance-of-genomic-stability
#19
Ramesh Kumar, Cheok Chit Fang
RIF1 plays a key role in inhibiting DNA end resection and promoting NHEJ mediated DNA double stand break repair in G1. However, whether SUMOlyation may regulate RIF1 functions is still largely unknown. Here, we report that RIF1 is SUMOlyated in response to DNA damage. We identified PIAS4 as the primary SUMO E3 ligase required for the SUMOylation of RIF1 protein. Mammalian cells compromised of PIAS4 expression, show impaired RIF1 SUMOylation and defective for the disassembly of DNA damage responsive RIF1 foci...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29187878/uhrf1-is-an-independent-prognostic-factor-and-a-potential-therapeutic-target-of-esophageal-squamous-cell-carcinoma
#20
Jiecheng Ye, Yong Zhang, Weiye Liang, Jianxian Huang, Lihui Wang, Xueyun Zhong
Purpose: Ubiquitin-like with plant homeodomain and ring-finger domains 1 (UHRF1) plays an essential role in DNA methylation, and the overexpression of UHRF1 is associated with poor prognosis in various cancers. Esophageal squamous cell carcinoma (ESCC) accounts for approximately 90% of esophageal cancer cases in China, but the five-year survival rate for patients is less than 10% due to limited clinical approaches for early diagnosis and treatment. The present research aimed to investigate the expression of UHRF1 in ESCC and its biological role in ESCC development...
2017: Journal of Cancer
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