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Monoubiquitination

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https://www.readbyqxmd.com/read/28091961/-1-h-13-c-and-15-n-backbone-and-side-chain-resonance-assignments-of-the-znf-ubp-domain-of-usp20-vdu2
#1
Yuanyuan Yang, Yi Wen, Naixia Zhang
Deubiquitinase USP20/VDU2 has been identified as a regulator of multiple proteins including hypoxia-inducible factor (HIF)-1α, β2-adrenergic receptor, and tumor necrosis factor receptor associated factor 6 etc. It contains four structural domains, including an N-terminal zinc-finger ubiquitin binding domain (ZnF-UBP) that potentially helps USP20 to recruit its ubiquitin substrates. Here we report the (1)H, (13)C and (15)N backbone and side-chain resonance assignments of the ZnF-UBP domain of USP20/VDU2. The BMRB accession number is 26901...
January 13, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28049720/icap-1-monoubiquitination-coordinates-matrix-density-and-rigidity-sensing-for-cell-migration-through-rock2-mrck%C3%AE-balance
#2
Anne-Pascale Bouin, Alexander Kyurmurkov, Myriam Régent-Kloeckner, Anne-Sophie Ribba, Eva Faurobert, Henri-Noël Fournier, Ingrid Bourrin-Reynard, Sandra Manet-Dupé, Christiane Oddou, Martial Balland, Emmanuelle Planus, Corinne Albiges-Rizo
Cell migration is a complex process requiring density and rigidity sensing of the microenvironment to adapt cell migratory speed through focal adhesion and actin cytoskeleton regulation. ICAP-1, a β1 integrin partner, is essential for ensuring integrin activation cycle and focal adhesion formation. We show that ICAP-1 is monoubiquitinated by Smurf1, preventing ICAP-1 binding to β1 integrin. The non-ubiquitinable form of ICAP-1 modifies β1 integrin focal adhesion organization and interferes with fibronectin density sensing...
January 3, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28032293/spatiotemporal-patterns-of-ring1-expression-after-rat-spinal-cord-injury
#3
Hanzhang Liu, Wei Ji, Peipei Gong, Chun Liu, Chengwei Duan, Yilu Gao, Xiaojuan Liu, Dongmei Zhang, Shunxing Zhu, Leilei Gong
Ring finger protein 1 (RING1) is a RING domain characterized protein belonging to the RING finger family. It is an E3 ubiquitin-protein ligase that mediated monoubiquitination of histone H2A and the core component of PRC1 complex, which is the repressive multiprotein complex of Polycomb group (PcG). Previous studies showed the important tumorigenic role of RING1 via promoting cell proliferation and the crucial function in maintaining transcriptional program stability during development. However, its mechanism for spinal cord injury (SCI) is still unknown...
December 28, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/28024295/characterization-of-two-novel-fancg-mutations-in-indian-fanconi-anemia-patients
#4
Avani Solanki, C Kumar Selvaa, Frenny Sheth, Nita Radhakrishnan, Manas Kalra, Babu Rao Vundinti
FA is a rare recessive genetic disorder with autosomal or X-linked mode of inheritance and is associated with 19 different FA complementation groups. We have studied three patients clinically diagnosed as FA. All three patients showed a high frequency chromosomal breakage in MMC induced blood cultures and FANCD2 non-monoubiquitination by western blotting. The molecular analysis using direct sequencing revealed two novel mutations in FANCG; 2 novel mutations c.1143+5G>C and c.883dupG, and a reported mutation c...
November 29, 2016: Leukemia Research
https://www.readbyqxmd.com/read/27999174/the-histone-deubiquitinase-otld1-targets-euchromatin-to-regulate-plant-growth
#5
Ido Keren, Vitaly Citovsky
Histone monoubiquitination is associated with active chromatin and plays an important role in epigenetic regulation of gene expression in plants. Deubiquitinating enzymes remove the ubiquitin group from histones and thereby contribute to gene repression. The Arabidopsis thaliana genome encodes 50 deubiquitinases, yet only 2 of them-UBP26 and OTLD1, members of the USP/UBP (ubiquitin-specific protease and ubiquitin-binding protein) and OTU (ovarian tumor protease) deubiquitinase families-are known to target histones...
December 20, 2016: Science Signaling
https://www.readbyqxmd.com/read/27986371/mechanism-of-ubiquitination-and-deubiquitination-in-the-fanconi-anemia-pathway
#6
Sylvie van Twest, Vincent J Murphy, Charlotte Hodson, Winnie Tan, Paolo Swuec, Julienne J O'Rourke, Jörg Heierhorst, Wayne Crismani, Andrew J Deans
Monoubiquitination and deubiquitination of FANCD2:FANCI heterodimer is central to DNA repair in a pathway that is defective in the cancer predisposition syndrome Fanconi anemia (FA). The "FA core complex" contains the RING-E3 ligase FANCL and seven other essential proteins that are mutated in various FA subtypes. Here, we purified recombinant FA core complex to reveal the function of these other proteins. The complex contains two spatially separate FANCL molecules that are dimerized by FANCB and FAAP100. FANCC and FANCE act as substrate receptors and restrict monoubiquitination to the FANCD2:FANCI heterodimer in only a DNA-bound form...
December 9, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27927750/mdm2-as-a-chromatin-modifier
#7
REVIEW
Magdalena Wienken, Ute M Moll, Matthias Dobbelstein
Mdm2 is the key negative regulator of the tumour suppressor p53, making it an attractive target for anti-cancer drug design. We recently identified a new role of Mdm2 in gene repression through its direct interaction with several proteins of the polycomb group (PcG) family. PcG proteins form polycomb repressive complexes PRC1 and PRC2. PRC2 (via EZH2) mediates histone 3 lysine 27 (H3K27) trimethylation, and PRC1 (via RING1B) mediates histone 2A lysine 119 (H2AK119) monoubiquitination. Both PRCs mostly support a compact and transcriptionally silent chromatin structure...
November 9, 2016: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27923209/recognition-of-ubiquitinated-nucleosomes
#8
REVIEW
Michael T Morgan, Cynthia Wolberger
Histone ubiquitination plays a non-degradative role in regulating transcription and the DNA damage response. A mechanistic understanding of this chromatin modification has lagged that of small histone modifications because of the technical challenges in preparing ubiquitinated nucleosomes. The recent structure of the DUB module of the SAGA coactivator complex bound to a nucleosome containing monoubiquitinated H2B has provided the first view of how specialized subunits target this enzyme to its substrate. Single particle electron microscopy of the intact SAGA coactivator suggests how the DUB module and histone acetyltransferase module engage a nucleosomal substrate...
December 3, 2016: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/27906959/pcna-dependent-cleavage-and-degradation-of-sde2-regulates-response-to-replication-stress
#9
Ukhyun Jo, Winson Cai, Jingming Wang, Yoojin Kwon, Alan D D'Andrea, Hyungjin Kim
Maintaining genomic integrity during DNA replication is essential for cellular survival and for preventing tumorigenesis. Proliferating cell nuclear antigen (PCNA) functions as a processivity factor for DNA replication, and posttranslational modification of PCNA plays a key role in coordinating DNA repair against replication-blocking lesions by providing a platform to recruit factors required for DNA repair and cell cycle control. Here, we identify human SDE2 as a new genome surveillance factor regulated by PCNA interaction...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27879315/monoubiquitination-inhibits-the-actin-bundling-activity-of-fascin
#10
Shengchen Lin, Shuang Lu, Mentor Mulaj, Bin Fang, Tyler Keeley, Lixin Wan, Jihui Hao, Martin Muschol, Jianwei Sun, Shengyu Yang
Fascin is an actin bundling protein that cross-links individual actin filaments into straight, compact, and stiff bundles, which are crucial for the formation of filopodia, stereocillia, and other finger-like membrane protrusions. The dysregulation of fascin has been implicated in cancer metastasis, hearing loss, and blindness. Here we identified monoubiquitination as a novel mechanism that regulates fascin bundling activity and dynamics. The monoubiquitination sites were identified to be Lys(247) and Lys(250), two residues located in a positive charge patch at the actin binding site 2 of fascin...
December 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27844253/the-role-of-deubiquitinases-in-breast-cancer
#11
Zhenna Xiao, Peijing Zhang, Li Ma
Although growing numbers of oncoproteins and pro-metastatic proteins have been extensively characterized, many of these tumor-promoting proteins are not good drug targets, which represent a major barrier to curing breast cancer and other cancers. There is a need, therefore, for alternative therapeutic approaches to destroying cancer-promoting proteins. The human genome encodes approximately 100 deubiquitinating enzymes (DUBs, also called deubiquitinases), which are amenable to pharmacologic inhibition by small molecules...
December 2016: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/27798111/the-ring-finger-domain-e3-ubiquitin-ligases-brca1-and-the-rnf20-rnf40-complex-in-global-loss-of-the-chromatin-mark-histone-h2b-monoubiquitination-h2bub1-in-cell-line-models-and-primary-high-grade-serous-ovarian-cancer
#12
Kristie-Ann Dickson, Alexander J Cole, Anthony J Gill, Adele Clarkson, Gregory B Gard, Angela Chou, Catherine J Kennedy, Beric R Henderson, Sian Fereday, Nadia Traficante, Kathryn Alsop, David D Bowtell, Anna deFazio, Roderick Clifton-Bligh, Deborah J Marsh
Enzymatic factors driving cancer-associated chromatin remodelling are of increasing interest as the role of the cancer epigenome in gene expression and DNA repair processes becomes elucidated. Monoubiquitination of histone H2B at lysine 120 (H2Bub1) is a central histone modification that functions in histone cross-talk, transcriptional elongation, DNA repair, maintaining centromeric chromatin and replication-dependent histone mRNA 3'-end processing, as well as being required for the differentiation of stem cells...
October 25, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27797324/-atypical-ubiquitination-of-proteins
#13
REVIEW
O A Buneeva, A E Medvedev
Ubiquitination is a type of posttranslational modification of intracellular proteins characterized by covalent attachment of one (monoubiquitination) or several (polyubiquitination) of ubiquitin molecules to target proteins. In the case of polyubiquitination, linear or branched polyubiquitin chains are formed. Their formation involves various lysine residues of monomeric ubiquitin. The best studied is Lys48-polyubiquitination, which targets proteins for proteasomal degradation. In this review we have considered examples of so-called atypical polyubiquitination, which mainly involves other lysine residues (Lys6, Lys11, Lys27, Lys29, Lys33, Lys63) and also N-terminal methionine...
July 2016: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/27793053/epigenetic-regulation-of-cancer-biology-and-anti-tumor-immunity-by-ezh2
#14
Anthos Christofides, Theodoros Karantanos, Kankana Bardhan, Vassiliki A Boussiotis
Polycomb group proteins regulate chromatin structure and have an important regulatory role on gene expression in various cell types. Two polycomb group complexes (Polycomb repressive complex 1 (PRC1) and 2 (PRC2)) have been identified in mammalian cells. Both PRC1 and PRC2 compact chromatin, and also catalyze histone modifications. PRC1 mediates monoubiquitination of histone H2A, whereas PRC2 catalyzes methylation of histone H3 on lysine 27. These alterations of histones can lead to altered gene expression patterns by regulating chromatin structure...
October 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27789696/histone-h2b-monoubiquitination-is-a-critical-epigenetic-switch-for-the-regulation-of-autophagy
#15
Su Chen, Yuanya Jing, Xuan Kang, Lu Yang, Da-Liang Wang, Wei Zhang, Lei Zhang, Ping Chen, Jian-Feng Chang, Xiao-Mei Yang, Fang-Lin Sun
Autophagy is an evolutionarily conserved cellular process that primarily participates in lysosome-mediated protein degradation. Although autophagy is a cytoplasmic event, how epigenetic pathways are involved in the regulation of autophagy remains incompletely understood. Here, we found that H2B monoubiquitination (H2Bub1) is down-regulated in cells under starvation conditions and that the decrease in H2Bub1 results in the activation of autophagy. We also identified that the deubiquitinase USP44 is responsible for the starvation-induced decrease in H2Bub1...
October 26, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27773819/fancd2-protects-against-bone-marrow-injury-from-ferroptosis
#16
Xinxin Song, Yangchun Xie, Rui Kang, Wen Hou, Xiaofang Sun, Michael W Epperly, Joel S Greenberger, Daolin Tang
Bone marrow injury remains a serious concern in traditional cancer treatment. Ferroptosis is an iron- and oxidative-dependent form of regulated cell death that has become part of an emerging strategy for chemotherapy. However, the key regulator of ferroptosis in bone marrow injury remains unknown. Here, we show that Fanconi anemia complementation group D2 (FANCD2), a nuclear protein involved in DNA damage repair, protects against ferroptosis-mediated injury in bone marrow stromal cells (BMSCs). The classical ferroptosis inducer erastin remarkably increased the levels of monoubiquitinated FANCD2, which in turn limited DNA damage in BMSCs...
October 20, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27773793/homocysteine-inhibits-neural-stem-cells-survival-by-inducing-dna-interstrand-cross-links-via-oxidative-stress
#17
Dan Wang, Yi-Ming Chen, Miao-Hua Ruan, Ai-Hua Zhou, Yan Qian, Chao Chen
Elevated plasma levels of homocysteine have been implicated in neurodevelopmental and neurodegenerative disorders in human studies. Although the molecular mechanisms underlying the effects of homocysteine (Hcy) cytotoxicity on the nervous system are not yet fully unknown, induction of DNA interstrand cross-links and inhibition of neural stem cells (NSCs) survival may be involved. The objective of our study was to investigate the effects of Hcy on DNA interstrand cross-links in NSCs, and to explore its possible mechanisms...
December 2, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27753536/pcna-ub-polyubiquitination-inhibits-cell-proliferation-and-induces-cell-cycle-checkpoints
#18
Zhoushuai Qin, Zhiqiang Bai, Ying Sun, Xiaohong Niu, Wei Xiao
In response to replication-blocking lesions, proliferating cell nuclear antigen (PCNA) can be sequentially ubiquitinated at the K164 residue leading to 2 modes of DNA-damage tolerance, namely translesion DNA synthesis (TLS) and error-free lesion bypass. Ectopic expression of PCNA fused with ubiquitin (Ub) lacking the 2 C-terminal Gly residues resembles PCNA monoubiquitination-mediated TLS. However, if the fused Ub contains C-terminal Gly residues, it is further polyubiquitinated and inhibits cell proliferation...
December 16, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27732584/molecular-basis-of-lys11-polyubiquitin-specificity-in-the-deubiquitinase-cezanne
#19
Tycho E T Mevissen, Yogesh Kulathu, Monique P C Mulder, Paul P Geurink, Sarah L Maslen, Malte Gersch, Paul R Elliott, John E Burke, Bianca D M van Tol, Masato Akutsu, Farid El Oualid, Masato Kawasaki, Stefan M V Freund, Huib Ovaa, David Komander
The post-translational modification of proteins with polyubiquitin regulates virtually all aspects of cell biology. Eight distinct chain linkage types co-exist in polyubiquitin and are independently regulated in cells. This 'ubiquitin code' determines the fate of the modified protein. Deubiquitinating enzymes of the ovarian tumour (OTU) family regulate cellular signalling by targeting distinct linkage types within polyubiquitin, and understanding their mechanisms of linkage specificity gives fundamental insights into the ubiquitin system...
October 20, 2016: Nature
https://www.readbyqxmd.com/read/27730210/maintenance-of-leukemic-cell-identity-by-the-activity-of-the-polycomb-complex-prc1-in-mice
#20
Alessandra Rossi, Karin J Ferrari, Andrea Piunti, SriGanesh Jammula, Fulvio Chiacchiera, Luca Mazzarella, Andrea Scelfo, Pier Giuseppe Pelicci, Diego Pasini
Leukemia is a complex heterogeneous disease often driven by the expression of oncogenic fusion proteins with different molecular and biochemical properties. Whereas several fusion proteins induce leukemogenesis by activating Hox gene expression (Hox-activating fusions), others impinge on different pathways that do not involve the activation of Hox genes (non-Hox-activating fusions). It has been postulated that one of the main oncogenic properties of the HOXA9 transcription factor is its ability to control the expression of the p16/p19 tumor suppressor locus (Cdkn2a), thereby compensating Polycomb-mediated repression, which is dispensable for leukemias induced by Hox-activating fusions...
October 2016: Science Advances
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