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Monoubiquitination

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https://www.readbyqxmd.com/read/28636932/ubiquitination-linked-phosphorylation-of-the-fanci-s-tq-cluster-contributes-to-activation-of-the-fanconi-anemia-i-d2-complex
#1
Ronald S Cheung, Maria Castella, Antonio Abeyta, Philip R Gafken, Nyka Tucker, Toshiyasu Taniguchi
Repair of interstrand crosslinks by the Fanconi anemia (FA) pathway requires both monoubiquitination and de-ubiquitination of the FANCI/FANCD2 (FANCI/D2) complex. In the standing model, the phosphorylation of six sites in the FANCI S/TQ cluster domain occurs upstream of, and promotes, FANCI/D2 monoubiquitination. We generated phospho-specific antibodies against three different S/TQ cluster sites (serines 556, 559, and 565) on human FANCI and found that, in contrast to the standing model, distinct FANCI sites were phosphorylated either predominantly upstream (ubiquitination independent; serine 556) or downstream (ubiquitination-linked; serines 559 and 565) of FANCI/D2 monoubiquitination...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28604766/the-deubiquitinating-enzymes-usp4-and-usp17-target-hyaluronan-synthase-2-and-differentially-affect-its-function
#2
M Mehić, V K de Sa, S Hebestreit, C-H Heldin, P Heldin
The levels of hyaluronan, a ubiquitous glycosaminoglycan prominent in the extracellular matrix, is balanced through the actions of hyaluronan-synthesizing enzymes (HAS1, 2 and 3) and degrading hyaluronidases (Hyal 1, 2, 3 and PH20). Hyaluronan accumulates in rapidly remodeling tissues, such as breast cancer, due to deregulated expression of the HAS2 gene and/or alterations of HAS2 activity. The activity of HAS2 is regulated by post-translational modifications, including ubiquitination. In order to identify deubiquitinating enzymes (DUBs) that are involved in de-ubiquitination of HAS2, a complementary (cDNA) library of 69 Flag-HA-tagged human DUBs cloned into retroviral vectors was screened in human embryonic kidney (HEK) 293T cells for their ability to de-ubiquitinate myc-tagged HAS2...
June 12, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28596781/polycomb-group-proteins-ring1a-and-ring1b-regulate-the-vegetative-phase-transition-in-arabidopsis
#3
Jian Li, Zheng Wang, Yugang Hu, Ying Cao, Ligeng Ma
Polycomb group (PcG) protein-mediated gene silencing is a major regulatory mechanism in higher eukaryotes that affects gene expression at the transcriptional level. Here, we report that two conserved homologous PcG proteins, RING1A and RING1B (RING1A/B), are required for global H2A monoubiquitination (H2Aub) in Arabidopsis. The mutation of RING1A/B increased the expression of members of the SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) gene family and caused an early vegetative phase transition. The early vegetative phase transition observed in ring1a ring1b double mutant plants was dependent on an SPL family gene, and the H2Aub status of the chromatin at SPL locus was dependent on RING1A/B...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28536288/cnot4-mediated-ubiquitination-of-influenza-a-virus-nucleoprotein-promotes-viral-rna-replication
#4
Yu-Chen Lin, King-Song Jeng, Michael M C Lai
Influenza A virus (IAV) RNA segments are individually packaged with viral nucleoprotein (NP) and RNA polymerases to form a viral ribonucleoprotein (vRNP) complex. We previously reported that NP is a monoubiquitinated protein which can be deubiquitinated by a cellular ubiquitin protease, USP11. In this study, we identified an E3 ubiquitin ligase, CNOT4 (Ccr4-Not transcription complex subunit 4), which can ubiquitinate NP. We found that the levels of viral RNA, protein, viral particles, and RNA polymerase activity in CNOT4 knockdown cells were lower than those in the control cells upon IAV infection...
May 23, 2017: MBio
https://www.readbyqxmd.com/read/28535142/srs2-promotes-synthesis-dependent-strand-annealing-by-disrupting-dna-polymerase-%C3%AE-extending-d-loops
#5
Jie Liu, Christopher Ede, William D Wright, Steven K Gore, Shirin S Jenkins, Bret D Freudenthal, M Todd Washington, Xavier Veaute, Wolf-Dietrich Heyer
Synthesis-dependent strand annealing (SDSA) is the preferred mode of homologous recombination in somatic cells leading to an obligatory non-crossover outcome, thus avoiding the potential for chromosomal rearrangements and loss of heterozygosity. Genetic analysis identified the Srs2 helicase as a prime candidate to promote SDSA. Here, we demonstrate that Srs2 disrupts D-loops in an ATP-dependent fashion and with a distinct polarity. Specifically, we partly reconstitute the SDSA pathway using Rad51, Rad54, RPA, RFC, DNA Polymerase δ with different forms of PCNA...
May 23, 2017: ELife
https://www.readbyqxmd.com/read/28535027/arsenite-binds-to-the-ring-finger-domain-of-fancl-e3-ubiquitin-ligase-and-inhibits-dna-interstrand-crosslink-repair
#6
Ji Jiang, Marina Bellani, Lin Li, Pengcheng Wang, Michael M Seidman, Yinsheng Wang
Human exposure to arsenic in drinking water is known to be associated with the development of bladder, lung, kidney, and skin cancers. The molecular mechanisms underlying the carcinogenic effects of arsenic species remain incompletely understood. DNA interstrand cross-links (ICLs) are among the most cytotoxic type of DNA lesions that block DNA replication and transcription, and these lesions can be induced by endogenous metabolism and by exposure to exogenous agents. Fanconi anemia (FA) is a congenital disorder manifested with elevated sensitivity toward DNA interstrand cross-linking agents, and monoubiquitination of FANCD2 by FANCL is a crucial step in FA-mediated DNA repair...
June 1, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28515150/receptor-for-advanced-glycation-end-products-is-targeted-by-fbxo10-for-ubiquitination-and-degradation
#7
John Evankovich, Travis Lear, Alison Mckelvey, Sarah Dunn, James Londino, Yuan Liu, Bill B Chen, Rama K Mallampalli
The receptor for advanced glycation end products (RAGE) is a highly expressed cell membrane receptor serving to anchor lung epithelia to matrix components, and it also amplifies inflammatory signaling during acute lung injury. However, mechanisms that regulate its protein concentrations in cells remain largely unknown. Here we show that RAGE exhibits an extended life span in lung epithelia (t½ 6 h), is monoubiquitinated at K374, and is degraded in lysosomes. The RAGE ligand ODN2006, a synthetic oligodeoxynucleotide resembling pathogenic hypomethylated CpG DNA, promotes rapid lysosomal RAGE degradation through activation of protein kinase C zeta (PKCζ), which phosphorylates RAGE...
May 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28498721/mechanisms-of-deubiquitinase-specificity-and-regulation
#8
Tycho E T Mevissen, David Komander
Protein ubiquitination is one of the most powerful posttranslational modifications of proteins, as it regulates a plethora of cellular processes in distinct manners. Simple monoubiquitination events coexist with more complex forms of polyubiquitination, the latter featuring many different chain architectures. Ubiquitin can be subjected to further posttranslational modifications (e.g., phosphorylation and acetylation) and can also be part of mixed polymers with ubiquitin-like modifiers such as SUMO (small ubiquitinrelated modifier) or NEDD8 (neural precursor cell expressed, developmentally downregulated 8)...
May 12, 2017: Annual Review of Biochemistry
https://www.readbyqxmd.com/read/28493408/monoubiquitination-joins-polyubiquitination-as-an-esteemed-proteasomal-targeting-signal
#9
REVIEW
Ido Livneh, Yelena Kravtsova-Ivantsiv, Ori Braten, Yong Tae Kwon, Aaron Ciechanover
A polyubiquitin chain attached covalently to the target substrate has been recognized for long as the "canonical" proteasomal degradation signal. However, several proteins have been shown to be targeted for degradation following monoubiquitination, indicating that the proteasome can recognize signals other than a ubiquitin polymer. A comprehensive screen aiming at determining the extent of this mode of recognition revealed that ∼40% of mammalian and ∼20% of yeast proteins are degraded following monoubiquitination...
June 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28493158/common-variable-immunodeficiency-caused-by-fanc-mutations
#10
Yujin Sekinaka, Noriko Mitsuiki, Kohsuke Imai, Miharu Yabe, Hiromasa Yabe, Kanako Mitsui-Sekinaka, Kenichi Honma, Masatoshi Takagi, Ayako Arai, Kenichi Yoshida, Yusuke Okuno, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Hideki Muramatsu, Seiji Kojima, Asuka Hira, Minoru Takata, Osamu Ohara, Seishi Ogawa, Tomohiro Morio, Shigeaki Nonoyama
Common variable immunodeficiency (CVID) is the most common adult-onset primary antibody deficiency disease due to various causative genes. Several genes, which are known to be the cause of different diseases, have recently been reported as the cause of CVID in patients by performing whole exome sequencing (WES) analysis. Here, we found FANC gene mutations as a cause of adult-onset CVID in two patients. B cells were absent and CD4(+) T cells were skewed toward CD45RO(+) memory T cells. T-cell receptor excision circles (TRECs) and signal joint kappa-deleting recombination excision circles (sjKRECs) were undetectable in both patients...
May 11, 2017: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28490629/pharmacological-targeting-of-rad6-enzyme-mediated-translesion-synthesis-overcomes-resistance-to-platinum-based-drugs
#11
Matthew A Sanders, Brittany Haynes, Pratima Nangia-Makker, Lisa A Polin, Malathy P Shekhar
Platinum drug-induced crosslink repair requires the concerted activities of translesion synthesis (TLS), Fanconi anemia (FA) and homologous recombination repair pathways. The E2 ubiquitin-conjugating enzyme Rad6 is essential for TLS. Here, we show that Rad6 plays a universal role in platinum-based drug tolerance. Using a novel Rad6-selective small molecule inhibitor (SMI#9) targeting the Rad6 catalytic site, we demonstrate that SMI#9 potentiates the sensitivities of cancer cells with innate or acquired cisplatin or oxaliplatin resistance...
May 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28481029/loss-of-h2b-monoubiquitination-is-associated-with-poor-differentiation-and-enhanced-malignancy-of-lung-adenocarcinoma
#12
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/28475871/aging-triggers-cytoplasmic-depletion-and-nuclear-translocation-of-the-e3-ligase-mahogunin-a%C3%A2-function-for-ubiquitin-in-neuronal-survival
#13
Stefano Benvegnù, María Inés Mateo, Ernest Palomer, Jerónimo Jurado-Arjona, Carlos G Dotti
A decline in proteasome function is causally connected to neuronal aging and aging-associated neuropathologies. By using hippocampal neurons in culture and in vivo, we show that aging triggers a reduction and a cytoplasm-to-nucleus redistribution of the E3 ubiquitin ligase mahogunin (MGRN1). Proteasome impairment induces MGRN1 monoubiquitination, the key post-translational modification for its nuclear entry. One potential mechanism for MGRN1 monoubiquitination is via progressive deubiquitination at the proteasome of polyubiquitinated MGRN1...
May 4, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28468752/usp4-inhibits-smad4-monoubiquitination-and-promotes-activin-and-bmp-signaling
#14
Fangfang Zhou, Feng Xie, Ke Jin, Zhengkui Zhang, Marcello Clerici, Rui Gao, Maarten van Dinther, Titia K Sixma, Huizhe Huang, Long Zhang, Peter Ten Dijke
SMAD4 is a common intracellular effector for TGF-β family cytokines, but the mechanism by which its activity is dynamically regulated is unclear. We demonstrated that ubiquitin-specific protease (USP) 4 strongly induces activin/BMP signaling by removing the inhibitory monoubiquitination from SMAD4. This modification was triggered by the recruitment of the E3 ligase, SMURF2, to SMAD4 following ligand-induced regulatory (R)-SMAD-SMAD4 complex formation. Whereas the interaction of the negative regulator c-SKI inhibits SMAD4 monoubiquitination, the ligand stimulates the recruitment of SMURF2 to the c-SKI-SMAD2 complex and triggers c-SKI ubiquitination and degradation...
June 1, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28453430/h2b-monoubiquitination-t-ub-or-not-t-ub-for-inducible-enhancers
#15
Gregory Segala, Didier Picard
Recently, we reported the unexpected finding that the monoubiquitination of histone H2B (H2Bub1) regulates inducible enhancers. Here, we propose a conceptual framework to reconcile the apparently discrepant roles of H2Bub1 in transcription initiation and elongation, and we discuss how H2Bub1 could regulate cellular processes linked to non-coding transcription.
March 15, 2017: Transcription
https://www.readbyqxmd.com/read/28434780/total-chemical-synthesis-of-methylated-analogues-of-histone-3-revealed-kdm4d-as-a-potential-regulator-of-h3k79me3
#16
Muhammad Jbara, Noga Guttmann-Raviv, Suman Kumar Maity, Nabieh Ayoub, Ashraf Brik
Histone H3 methylation plays an important role in regulating gene expression. In histones in general, this mark is dynamically regulated via various demethylases, which found to control cell fate decisions as well as linked to several diseases, including neurological and cancer. Despite major progress in studying methylation mark at various positions in H3 histone proteins, less is known about the regulation of methylated H3 at Lys79. Methylation at this site is known to have direct cross-talk with monoubiquitination of histone H2B at positions Lys120 and 34, as well as with acetylated H3 at Lys9...
April 12, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28431276/enzymatic-activity-gene-expression-and-posttranslational-modifications-of-photosynthetic-and-non-photosynthetic-phosphoenolpyruvate-carboxylase-in-ammonium-stressed-sorghum-plants
#17
Cirenia Arias-Baldrich, Clara de la Osa, Nadja Bosch, Isabel Ruiz-Ballesta, José A Monreal, Sofía García-Mauriño
Sorghum plants grown with 5mM (NH4)2SO4 showed symptoms of stress, such as reduced growth and photosynthesis, leaf chlorosis, and reddish roots. Phosphoenolpyruvate carboxylase (PEPC) activity, by supplying carbon skeletons for ammonium assimilation, plays a pivotal role in tolerance to ammonium stress. This work investigated the effect of ammonium nutrition on PPC and PPCK gene expression, on PEPC activity, and on post-translational modifications (PTMs) of PEPC in leaves and roots of sorghum plants. Ammonium increased PEPC kinase (PEPCk) activity and the phosphorylation state of PEPC in leaves, both in light and in the dark, due to increased PPCK1 expression in leaves...
July 2017: Journal of Plant Physiology
https://www.readbyqxmd.com/read/28430587/parkin-regulates-translesion-dna-synthesis-in-response-to-uv-radiation
#18
Xuefei Zhu, Xiaolu Ma, Yingfeng Tu, Min Huang, Hongmei Liu, Fengli Wang, Juanjuan Gong, Jiuqiang Wang, Xiaoling Li, Qian Chen, Hongyan Shen, Shu Zhu, Yun Wang, Yang Liu, Caixia Guo, Tie-Shan Tang
Deficiency of Parkin is a major cause of early-onset Parkinson's disease (PD). Notably, PD patients also exhibit a significantly higher risk in melanoma and other skin tumors, while the mechanism remains largely unknown. In this study, we show that depletion of Parkin causes compromised cell viability and genome stability after ultraviolet (UV) radiation. We demonstrate that Parkin promotes efficient Rad18-dependent proliferating cell nuclear antigen (PCNA) monoubiquitination by facilitating the formation of Replication protein A (RPA)-coated ssDNA upon UV radiation...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28407635/role-of-the-ubiquitin-c-terminal-hydrolase-l1-modulated-ubiquitin-proteasome-system-in-auditory-cortex-senescence
#19
Ya Zhang, Xiang Huang, Xue-Yan Zhao, Yu-Juan Hu, Hai-Ying Sun, Wei-Jia Kong
BACKGROUND/AIMS: According to recent studies, central auditory impairments are closely related to neurodegenerative diseases. However, the mechanism of central presbycusis remains unclear. Ubiquitin C-terminal hydrolase L1 (UCHL1) is important in maintaining proteasomal activity; however, the detailed mechanism has not yet been fully elucidated. This study aims to investigate the molecular alterations involved in UCHL1 regulation during auditory cortex aging. METHODS: D-Galactose (D-gal) induces oxidative stress and senescence in the auditory cortex, as reported in our previous studies...
2017: ORL; Journal for Oto-rhino-laryngology and its related Specialties
https://www.readbyqxmd.com/read/28403905/h2a-monoubiquitination-in-arabidopsis-thaliana-is-generally-independent-of-lhp1-and-prc2-activity
#20
Yue Zhou, Francisco J Romero-Campero, Ángeles Gómez-Zambrano, Franziska Turck, Myriam Calonje
BACKGROUND: Polycomb group complexes PRC1 and PRC2 repress gene expression at the chromatin level in eukaryotes. The classic recruitment model of Polycomb group complexes in which PRC2-mediated H3K27 trimethylation recruits PRC1 for H2A monoubiquitination was recently challenged by data showing that PRC1 activity can also recruit PRC2. However, the prevalence of these two mechanisms is unknown, especially in plants as H2AK121ub marks were examined at only a handful of Polycomb group targets...
April 12, 2017: Genome Biology
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