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Monoubiquitination

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https://www.readbyqxmd.com/read/28515150/receptor-for-advanced-glycation-end-products-is-targeted-by-fbxo10-for-ubiquitination-and-degradation
#1
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
#2
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
#3
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...
May 11, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28493158/common-variable-immunodeficiency-caused-by-fanc-mutations
#4
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
#5
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
#6
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
#7
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
#8
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...
May 3, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28453430/h2b-monoubiquitination-t-ub-or-not-t-ub-for-inducible-enhancers
#9
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
#10
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
#11
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...
March 31, 2017: Journal of Plant Physiology
https://www.readbyqxmd.com/read/28430587/parkin-regulates-translesion-dna-synthesis-in-response-to-uv-radiation
#12
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...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28407635/role-of-the-ubiquitin-c-terminal-hydrolase-l1-modulated-ubiquitin-proteasome-system-in-auditory-cortex-senescence
#13
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...
April 14, 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
#14
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
https://www.readbyqxmd.com/read/28373209/fludarabine-resistance-mediated-by-aminoglycoside-3-phosphotransferase-iia-and-the-structurally-related-eukaryotic-camp-dependent-protein-kinase
#15
Dámaso Sánchez-Carrera, Sara Bravo-Navas, Elena Cabezón, Ignacio Arechaga, Matilde Cabezas, Lucrecia Yáñez, Carlos Pipaón
While working with G418-resistant stably transfected cells, we realized the neomycin resistance gene (NeoR), which encodes the aminoglycoside-3'-phosphotransferase-IIa [APH(3')-IIa], also confers resistance to the nucleoside analog fludarabine. Fludarabine is a cytostatic drug widely used in the treatment of hematologic and solid tumors as well as in the conditioning of patients before transplantation of hematopoietic progenitors. We present evidence that NeoR-transfected cells do not incorporate fludarabine, thus avoiding DNA damage caused by the drug, evidenced by a lack of FANCD2 monoubiquitination and impaired apoptosis...
April 3, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28362432/regulation-of-transcriptional-activators-by-dna-binding-domain-ubiquitination
#16
Vivien Landré, Bhindu Revi, Maria Gil Mir, Chandra Verma, Ted R Hupp, Nick Gilbert, Kathryn L Ball
Ubiquitin is a key component of the regulatory network that maintains gene expression in eukaryotes, yet the molecular mechanism(s) by which non-degradative ubiquitination modulates transcriptional activator (TA) function is unknown. Here endogenous p53, a stress-activated transcription factor required to maintain health, is stably monoubiquitinated, following pathway activation by IR or Nutlin-3 and localized to the nucleus where it becomes tightly associated with chromatin. Comparative structure-function analysis and in silico modelling demonstrate a direct role for DNA-binding domain (DBD) monoubiquitination in TA activation...
May 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28353339/label-free-and-real-time-detection-of-protein-ubiquitination-with-a-biological-nanopore
#17
Carsten Wloka, Veerle Van Meervelt, Dewi van Gelder, Natasha Danda, Nienke Jager, Chris P Williams, Giovanni Maglia
The covalent addition of ubiquitin to target proteins is a key post-translational modification that is linked to a myriad of biological processes. Here, we report a fast, single-molecule, and label-free method to probe the ubiquitination of proteins employing an engineered Cytolysin A (ClyA) nanopore. We show that ionic currents can be used to recognize mono- and polyubiquitinated forms of native proteins under physiological conditions. Using defined conjugates, we also show that isomeric monoubiquitinated proteins can be discriminated...
March 29, 2017: ACS Nano
https://www.readbyqxmd.com/read/28351977/deltex2-represses-myod-expression-and-inhibits-myogenic-differentiation-by-acting-as-a-negative-regulator-of-jmjd1c
#18
Dan Luo, Antoine de Morree, Stephane Boutet, Navaline Quach, Vanita Natu, Arjun Rustagi, Thomas A Rando
The myogenic regulatory factor MyoD has been implicated as a key regulator of myogenesis, and yet there is little information regarding its upstream regulators. We found that Deltex2 inhibits myogenic differentiation in vitro, and that skeletal muscle stem cells from Deltex2 knockout mice exhibit precocious myogenic differentiation and accelerated regeneration in response to injury. Intriguingly, Deltex2 inhibits myogenesis by suppressing MyoD transcription, and the Deltex2 knockout phenotype can be rescued by a loss-of-function allele for MyoD In addition, we obtained evidence that Deltex2 regulates MyoD expression by promoting the enrichment of histone 3 modified by dimethylation at lysine 9 at a key regulatory region of the MyoD locus...
April 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28348081/the-herpes-simplex-virus-1-ul36usp-deubiquitinase-suppresses-dna-repair-in-host-cells-via-deubiquitination-of-proliferating-cell-nuclear-antigen
#19
Xiaodong Dong, Junhong Guan, Chunfu Zheng, Xiaofeng Zheng
Herpes simplex virus 1 (HSV-1) infection manipulates distinct host DNA damage responses (DDR) to facilitate virus proliferation, but the molecular mechanisms remain to be elucidated. One possible HSV-1 target might be DNA damage-tolerance mechanisms, such as the translesion synthesis (TLS) pathway. In TLS, proliferating cell nuclear antigen (PCNA) is monoubiquitinated in response to DNA damage-caused replication fork stalling. Ubiquitinated PCNA then facilitates the error-prone DNA polymerase eta (pol eta)-mediated TLS, allowing the fork to bypass damaged sites...
March 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28341648/dna-damage-tolerance-pathway-choice-through-uls1-modulation-of-srs2-sumoylation-in-saccharomyces-cerevisiae
#20
Karol Kramarz, Seweryn Mucha, Ireneusz Litwin, Anna Barg-Wojas, Robert Wysocki, Dorota Dziadkowiec
DNA damage tolerance and homologous recombination pathways function to bypass replication-blocking lesions and ensure completion of DNA replication. However, inappropriate activation of these pathways may lead to increased mutagenesis or formation of deleterious recombination intermediates, often leading to cell death or cancer formation in higher organisms. Post-translational modifications of PCNA regulate the choice of repair pathways at replication forks. Its monoubiquitination favors translesion synthesis, while polyubiquitination stimulates template switching...
May 2017: Genetics
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