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Monoubiquitination

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https://www.readbyqxmd.com/read/27923209/recognition-of-ubiquitinated-nucleosomes
#1
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
#2
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
#3
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 crosslinks 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 K247 and K250, two residues located in a positive charge patch at the actin binding site 2 (ABS2) of fascin...
November 22, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27844253/the-role-of-deubiquitinases-in-breast-cancer
#4
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...
November 14, 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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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 two 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 two 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...
October 18, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27732584/molecular-basis-of-lys11-polyubiquitin-specificity-in-the-deubiquitinase-cezanne
#12
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 12, 2016: Nature
https://www.readbyqxmd.com/read/27730210/maintenance-of-leukemic-cell-identity-by-the-activity-of-the-polycomb-complex-prc1-in-mice
#13
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
https://www.readbyqxmd.com/read/27707542/the-pol30-k196-residue-plays-a-critical-role-in-budding-yeast-dna-postreplication-repair-through-interaction-with-rad18
#14
Li Fan, Wei Xiao
PCNA plays critical roles in DNA replication and various DNA repair pathways including DNA damage tolerance (DDT). In budding yeast Saccharomyces cerevisiae, DDT (aka DNA postreplication repair, PRR) is achieved by sequential ubiquitination of PCNA encoded by POL30. Our previous studies revealed that two Arabidopsis PCNA genes were able to complement the essential function of POL30 in budding yeast, but failed to rescue the PRR activity. Here we hypothesize that a certain amino acid variation(s) is responsible for the difference, and identified K196 as a critical residue for the PRR activity...
September 22, 2016: DNA Repair
https://www.readbyqxmd.com/read/27693081/h2ak119-monoubiquitination-regulates-angiotensin-ii-receptor-mediated-macrophage-infiltration-and-renal-fibrosis-in-type-2-diabetic-rats
#15
Anuradha Pandey, Santosh Kumar Goru, Almesh Kadakol, Vajir Malek, Nisha Sharma, Anil Bhanudas Gaikwad
Monocyte chemoattractant protein (MCP-1) and transforming growth factor-β (TGF-β1)-markers of inflammation and fibrosis, are central to type 2 diabetic nephropathy (T2DN) progression. ow H2AK119Ub affects the expression of MCP-1 and TGF-β1 and their regulation by Angiotensin II receptor subtypes remains unknown. In the current study, we aimed to study the effect of Angiotensin II receptors' blockade on the macrophage infiltration and histone modifications occurring at the promoter region of Mcp1 and Tgfb1in high fat diet fed and low dose streptozotocin treated male Wistar rats...
September 27, 2016: Biochimie
https://www.readbyqxmd.com/read/27692985/monoubiquitination-of-histone-h2b-blocks-eviction-of-histone-variant-h2a-z-from-inducible-enhancers
#16
Gregory Segala, Marcela A Bennesch, Deo Prakash Pandey, Nicolas Hulo, Didier Picard
Covalent modifications of histones play a crucial role in the regulation of gene expression. Histone H2B monoubiquitination has mainly been described as a regulator of transcription elongation, but its role in transcription initiation is poorly documented. We investigated the role of this histone mark (H2Bub1) on different inducible enhancers, in particular those regulated by estrogen receptor α, by loss- and gain-of-function experiments with the specific E3-ubiquitin ligase complex of H2B: RNF20/RNF40. RNF20/RNF40 overexpression causes repression of the induced activity of these enhancers...
October 20, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27678051/role-of-e2-ring-interactions-in-governing-rnf4-mediated-substrate-ubiquitination
#17
Anthony DiBello, Ajit B Datta, Xiangbin Zhang, Cynthia Wolberger
Members of the really interesting new gene (RING) E3 ubiquitin ligase family bind to both substrate and ubiquitin-charged E2 enzyme, promoting the transfer of ubiquitin from the E2 to substrate. Either a single ubiquitin or one of the several types of polyubiquitin chains can be conjugated to substrate proteins, with different types of ubiquitin modifications signaling the distinct outcomes. E2 enzymes play a central role in governing the nature of the ubiquitin modification, although the essential features of the E2 that differentiate mono- versus polyubiquitinating E2 enzymes remain unclear...
November 20, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27630184/zrf1-chromatin-regulators-have-polycomb-silencing-and-independent-roles-in-development
#18
Jing Feng, Donghong Chen, Alexandre Berr, Wen-Hui Shen
Histone H2A monoubiquitination (H2Aub1), catalyzed by Polycomb Repressive Complex 1 (PRC1), is a key epigenetic mark in Polycomb silencing. However, little is known about how H2Aub1 is read to exert downstream physiological functions. The animal ZUOTIN RELATED FACTOR 1 (ZRF1) has been reported to bind H2Aub1 to promote or repress expression of varied target genes. Here we show that the Arabidopsis ZRF1 homologues, AtZRF1a and AtZRF1b, are key regulators of multiple processes during plant growth and development...
September 14, 2016: Plant Physiology
https://www.readbyqxmd.com/read/27601672/structural-mechanism-for-the-recognition-and-ubiquitination-of-a-single-nucleosome-residue-by-rad6-bre1
#19
Laura D Gallego, Medini Ghodgaonkar Steger, Anton A Polyansky, Tobias Schubert, Bojan Zagrovic, Ning Zheng, Tim Clausen, Franz Herzog, Alwin Köhler
Cotranscriptional ubiquitination of histone H2B is key to gene regulation. The yeast E3 ubiquitin ligase Bre1 (human RNF20/40) pairs with the E2 ubiquitin conjugating enzyme Rad6 to monoubiquitinate H2B at Lys123. How this single lysine residue on the nucleosome core particle (NCP) is targeted by the Rad6-Bre1 machinery is unknown. Using chemical cross-linking and mass spectrometry, we identified the functional interfaces of Rad6, Bre1, and NCPs in a defined in vitro system. The Bre1 RING domain cross-links exclusively with distinct regions of histone H2B and H2A, indicating a spatial alignment of Bre1 with the NCP acidic patch...
September 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27582499/histone-h2ak119-and-h2bk120-monoubiquitination-modulate-set7-9-and-suv39h1-in-type-1-diabetes-induced-renal-fibrosis
#20
Santosh Kumar Goru, Almesh Kadakol, Anuradha Pandey, Vajir Malek, Nisha Sharma, Anil Bhanudas Gaikwad
Hyperglycaemia-induced expression of extracellular matrix (ECM) components plays a major role in the development diabetic nephropathy (DN). The epigenetic mechanisms that modulate ECM gene expression in DN remain unclear. Therefore, we examined the role of histone H2A and H2B mono-ubiquitination on epigenetic chromatin marks such as histone H3 lysine dimethylation (H3K4Me2, H3K9Me2 and H3K79Me2) in type 1 diabetic rat kidney. Hyperglycaemia increased collagen deposition and Col1a1 gene expression. In whole kidney of diabetic animals, both H2AK119 mono-ubiquitination (H2AK119Ub) and H2BK120 mono-ubiquitination (H2BK120Ub) were found to be increased whereas, in glomeruli of diabetic animals expression of both H2AK119Ub and H2BK120Ub were reduced...
August 31, 2016: Biochemical Journal
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