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Monoubiquitination

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https://www.readbyqxmd.com/read/29317652/sirt6-dependent-cysteine-monoubiquitination-in-the-pre-set-domain-of-suv39h1-regulates-the-nf-%C3%AE%C2%BAb-pathway
#1
Irene Santos-Barriopedro, Laia Bosch-Presegué, Anna Marazuela-Duque, Carolina de la Torre, Carlota Colomer, Berta N Vazquez, Thomas Fuhrmann, Bárbara Martínez-Pastor, Wenfu Lu, Thomas Braun, Eva Bober, Thomas Jenuwein, Lourdes Serrano, Manel Esteller, Zhenbang Chen, Silvia Barceló-Batllori, Raúl Mostoslavsky, Lluis Espinosa, Alejandro Vaquero
Sirtuins are NAD+-dependent deacetylases that facilitate cellular stress response. They include SirT6, which protects genome stability and regulates metabolic homeostasis through gene silencing, and whose loss induces an accelerated aging phenotype directly linked to hyperactivation of the NF-κB pathway. Here we show that SirT6 binds to the H3K9me3-specific histone methyltransferase Suv39h1 and induces monoubiquitination of conserved cysteines in the PRE-SET domain of Suv39h1. Following activation of NF-κB signaling Suv39h1 is released from the IκBα locus, subsequently repressing the NF-κB pathway...
January 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29307785/meiotic-development-initiation-in-the-fungus-podospora-anserina-requires-the-peroxisome-receptor-export-machinery
#2
Fernando Suaste-Olmos, Claudia Zirión-Martínez, Harumi Takano-Rojas, Leonardo Peraza-Reyes
Peroxisomes are versatile organelles essential for diverse developmental processes. One such process is the meiotic development of Podospora anserina. In this fungus, absence of the docking peroxin PEX13, the RING-finger complex peroxins, or the PTS2 co-receptor PEX20 blocks sexual development before meiocyte formation. However, this defect is not seen in the absence of the receptors PEX5 and PEX7, or of the docking peroxins PEX14 and PEX14/17. Here we describe the function of the remaining uncharacterized P...
January 4, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29295930/identification-of-a-ubiquitin-binding-interface-using-rosetta-and-deer
#3
Maxx H Tessmer, David M Anderson, Adam M Pickrum, Molly O Riegert, Rocco Moretti, Jens Meiler, Jimmy B Feix, Dara W Frank
ExoU is a type III-secreted cytotoxin expressing A2 phospholipase activity when injected into eukaryotic target cells by the bacterium Pseudomonas aeruginosa The enzymatic activity of ExoU is undetectable in vitro unless ubiquitin, a required cofactor, is added to the reaction. The role of ubiquitin in facilitating ExoU enzymatic activity is poorly understood but of significance for designing inhibitors to prevent tissue injury during infections with strains of P. aeruginosa producing this toxin. Most ubiquitin-binding proteins, including ExoU, demonstrate a low (micromolar) affinity for monoubiquitin (monoUb)...
January 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29274341/the-ubiquitin-specific-protease-usp36-is-a-conserved-histone-h2b-deubiquitinase
#4
Tiffany DeVine, Rosalie C Sears, Mu-Shui Dai
Histone H2b monoubiquitination plays a critical role in the regulation of gene transcription. Deregulation of H2b monoubiquitination contributes to human pathologies, such as cancer. Here we report that human USP36 is a novel H2bub1 deubiquitinase. We show that USP36 interacts with H2b and deubiquitinates H2bub1 in cells and in vitro. Overexpression of USP36 markedly reduced the levels of H2bub1 in cells. Using the p21 gene as a model, we demonstrate that depletion of USP36 increases H2bub1 at the p21 locus, primarily within its gene body...
December 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29234344/lhp1-could-act-as-an-activator-and-a-repressor-of-transcription-in-plants
#5
REVIEW
Jing Feng, Jiang Lu
Polycomb group (PcG) proteins within the polycomb repressive complex 1 (PRC1) and PRC2 are significant epigenetic regulatory factors involved in important cellular and developmental processes in eukaryotes. In Arabidopsis, LIKE HETEROCHROMATIN PROTEIN 1 (LHP1), also known as TERMINAL FLOWER 2, has been proposed as a plant specific subunit of PRC1 that could bind the trimethylated lysine 27 of histone H3 (H3K27me3), which is established by PRC2 and is required for a functional plant PcG system. LHP1 not only interacts with PRC1 to catalyze monoubiquitination at lysine 119 of histone H2A but also functions with PRC2 to establish H3K27me3...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29231814/a-homozygous-fancm-mutation-underlies-a-familial-case-of-non-syndromic-primary-ovarian-insufficiency
#6
Baptiste Fouquet, Patrycja Pawlikowska, Sandrine Caburet, Celine Guigon, Marika Mäkinen, Laura Tanner, Marja Hietala, Kaja Urbanska, Laura Bellutti, Bérangère Legois, Bettina Bessieres, Alain Gougeon, Alexandra Benachi, Gabriel Livera, Filippo Rosselli, Reiner A Veitia, Micheline Misrahi
Primary Ovarian Insufficiency (POI) affects ~1% of women under forty. Exome sequencing of two Finnish sisters with non-syndromic POI revealed a homozygous mutation in FANCM, leading to a truncated protein (p.Gln1701*). FANCM is a DNA-damage response gene whose heterozygous mutations predispose to breast cancer. Compared to the mother's cells, the patients' lymphocytes displayed higher levels of basal and mitomycin C (MMC)-induced chromosomal abnormalities. Their lymphoblasts were hypersensitive to MMC and MMC-induced monoubiquitination of FANCD2 was impaired...
December 12, 2017: ELife
https://www.readbyqxmd.com/read/29185083/linear-ubiquitin-chain-induces-apoptosis-and-inhibits-tumor-growth
#7
Zhoushuai Qin, Wandong Jiang, Guifen Wang, Ying Sun, Wei Xiao
Ubiquitination of proliferating cell nuclear antigen (PCNA) plays an important role in DNA damage response. Ectopic expression of PCNA fused at either terminus with ubiquitin (Ub) lacking two C-terminal glycine residues induces translesion DNA synthesis which resembles synthesis mediated by PCNA monoubiquitination. PCNA fused with Ub containing the C-terminal Gly residues at the C-terminus can be further polyubiquitinated in a Gly-dependent manner, which inhibits cell proliferation and induces ATR-dependent replication checkpoint...
November 28, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29167336/an-insight-into-the-role-of-e3-ubiquitin-ligase-c-cbl-escrt-machinery-and-host-cell-signaling-in-kaposi-s-sarcoma-associated-herpesvirus-kshv-entry-and-trafficking
#8
Binod Kumar, Arunava Roy, Mohanan Valiya Veettil, Bala Chandran
Kaposi's sarcoma-associated herpesvirus (KSHV) in vitro infection of dermal endothelial cell begins with its binding to host cell surface receptor molecules such as heparan sulfate (HS), integrins (α3β1, αVβ3 and αVβ5), xCT and EphA2 receptor tyrosine kinase (EphA2R). These initial events initiate dynamic host protein-protein interactions involving a multi-molecular complex of receptors, signal molecules (FAK, Src, PI3-K, RhoA-GTPase), adaptors (c-Cbl, CIB1, Crk, p130Cas and GEF-C3G), and actin/myosin II light chain that leads to virus entry via macropinocytosis...
November 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29164995/novel-polyubiquitin-imaging-system-polyub-fc-reveals-that-k33-linked-polyubiquitin-is-recruited-by-sqstm1-p62
#9
Yoichi Nibe, Shigeru Oshima, Masanori Kobayashi, Chiaki Maeyashiki, Yu Matsuzawa, Kana Otsubo, Hiroki Matsuda, Emi Aonuma, Yasuhiro Nemoto, Takashi Nagaishi, Ryuichi Okamoto, Kiichiro Tsuchiya, Tetsuya Nakamura, Shinichiro Nakada, Mamoru Watanabe
Ubiquitin chains are formed with 8 structurally and functionally distinct polymers. However, the functions of each polyubiquitin remain poorly understood. We developed a polyubiquitin-mediated fluorescence complementation (PolyUb-FC) assay using Kusabira Green (KG) as a split fluorescent protein. The PolyUb-FC assay has the advantage that monoubiquitination is nonfluorescent and chain-specific poly-ubiquitination can be directly visualized in living cells without using antibodies. We applied the PolyUb-FC assay to examine K33-linked polyubiquitin...
November 22, 2017: Autophagy
https://www.readbyqxmd.com/read/29130659/-dna-repair-function-and-mutation-of-an-h2b-monoubiquitination-factor-wdr70-in-ovarian-cancer
#10
Zi-Zhi Tang, Hai-Bin Wang, Ming Zeng, Cong Liu, De-Hua Li
OBJECTIVE: To investigate the roles of enzyme DCAF proteinDNA damagebinding protein 1 (DDB1)/cullin4 (CRL4) complex family members CRL4WD40 repeat domain protein 70 (WDR70) in DNA repair process and its mutation in ovarian cancer. METHODS: Immunofluorescent assay was employed to measure H2AX (γH2AX) and phosphorylated replication protein A2 (RPA32) formed in siDDB1 or siWDR70 ovarian cancer cells after the treatments of chemical medicine and radioactive threapy...
September 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/29111344/the-crystal-structure-and-conformations-of-an-unbranched-mixed-tri-ubiquitin-chain-containing-k48-and-k63-linkages
#11
Prasanth Padala, Nadine Soudah, Moshe Giladi, Yoni Haitin, Michail N Isupov, Reuven Wiener
The ability of ubiquitin to function in a wide range of cellular processes is ascribed to its capacity to cause a diverse spectrum of modifications. While a target protein can be modified with monoubiquitin, it can also be modified with ubiquitin chains. The latter include seven types of homotypic chains as well as mixed ubiquitin chains. In a mixed chain, not all the isopeptide bonds are restricted to a specific lysine of ubiquitin, resulting in a chain possessing more than one type of linkage. While structural characterization of homotypic chains has been well elucidated, less is known about mixed chains...
October 27, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29100324/modulation-of-the-fanconi-anemia-pathway-via-chemically-induced-changes-in-chromatin-structure
#12
David A Vierra, Jada L Garzon, Meghan A Rego, Morganne M Adroved, Maurizio Mauro, Niall G Howlett
Fanconi anemia (FA) is a rare disease characterized by congenital defects, bone marrow failure, and atypically early-onset cancers. The FA proteins function cooperatively to repair DNA interstrand crosslinks. A major step in the activation of the pathway is the monoubiquitination of the FANCD2 and FANCI proteins, and their recruitment to chromatin-associated nuclear foci. The regulation and function of FANCD2 and FANCI, however, is poorly understood. In addition, how chromatin state impacts pathway activation is also unknown...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29093085/the-ubiquitin-proteasome-system-is-necessary-for-the-efficient-replication-of-human-astrovirus
#13
Luis A Casorla-Pérez, Tomás López, Susana López, Carlos F Arias
Astroviruses, members of the family Astroviridae, represent an important cause of human gastroenteritis in the world. The cellular factors required for astrovirus replication have been poorly studied. In this work, we evaluated the relevance of the ubiquitin-proteasome system (UPS) in the replication of Yuc8, a human astrovirus serotype 8 strain. We found that proteasome inhibitors decrease the production of infectious viral progeny at a step in the replication cycle subsequent to virus entry. The inhibition of the proteasome activity decreases viral RNA levels and viral protein synthesis; similarly, the inhibition of ubiquitination by chemical inhibitors or RNAi reduces the production of viral progeny as well as viral protein synthesis...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29059323/fanci-and-fancd2-have-common-as-well-as-independent-functions-during-the-cellular-replication-stress-response
#14
Elizabeth L Thompson, Jung E Yeo, Eun-A Lee, Yinan Kan, Maya Raghunandan, Constanze Wiek, Helmut Hanenberg, Orlando D Schärer, Eric A Hendrickson, Alexandra Sobeck
Fanconi anemia (FA) is an inherited cancer predisposition syndrome characterized by cellular hypersensitivity to DNA interstrand crosslinks (ICLs). To repair these lesions, the FA proteins act in a linear hierarchy: following ICL detection on chromatin, the FA core complex monoubiquitinates and recruits the central FANCI and FANCD2 proteins that subsequently coordinate ICL removal and repair of the ensuing DNA double-stranded break by homology-dependent repair (HDR). FANCD2 also functions during the replication stress response by mediating the restart of temporarily stalled replication forks thereby suppressing the firing of new replication origins...
November 16, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29058668/e3-ubiquitin-ligase-bre1-couples-sister-chromatid-cohesion-establishment-to-dna-replication-in-saccharomyces-cerevisiae
#15
Wei Zhang, Clarence Hue Lok Yeung, Liwen Wu, Karen Wing Yee Yuen
Bre1, a conserved E3 ubiquitin ligase in Saccharomyces cerevisiae, together with its interacting partner Lge1, are responsible for histone H2B monoubiquitination, which regulates transcription, DNA replication, DNA damage response and repair, ensuring the structural integrity of the genome. Deletion of BRE1 or LGE1 also results in whole chromosome instability. We discovered a novel role for Bre1, Lge1 and H2Bub1 in chromosome segregation and sister chromatid cohesion. Bre1's function in G1 and S phases contributes to cohesion establishment, but it is not required for cohesion maintenance in G2 phase...
October 23, 2017: ELife
https://www.readbyqxmd.com/read/29048607/the-arabidopsis-chromatin-remodeling-factor-chr5-regulates-plant-immune-responses-and-nucleosome-occupancy
#16
Baohong Zou, Qi Sun, Wenli Zhang, Yuan Ding, Dong-Lei Yang, Jian Hua
ATP-dependent chromatin remodeling factors use the energy of ATP hydrolysis to alter the structure of chromatin and are important regulators of eukaryotic gene expression. One such factor CHR5 (Chromatin Remodeling Factor 5) in Arabidopsis (Arabidopsis thaliana) was previously found to be involved in growth and development regulation. Here we show that CHR5 is required for the upregulation of the intracellular immune receptor gene SNC1 (SUPPRESSOR OF npr1-1, CONSTITUTIVE1) and consequently the autoimmunity induced by SNC1 upregulation...
October 17, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/29021208/constitutive-role-of-the-fanconi-anemia-d2-gene-in-the-replication-stress-response
#17
Yanyan Tian, Xi Shen, Rui Wang, Naeh Klages-Mundt, Erica J Lynn, Sara K Martin, Yin Ye, Min Gao, Junjie Chen, Katharina Schlacher, Lei Li
In response to DNA crosslinking damage, the Fanconi anemia (FA) core complex activates the FA pathway by monoubiquitinating Fanconi anemia complementation group D2 (FANCD2) for the initiation of the nucleolytic processing of the DNA crosslinks and stabilization of stalled replication forks. Given that all the classic FA proteins coordinately monoubiquitinate FANCD2, it is unclear why losses of individual classic FA genes yield varying cellular sensitivities to crosslinking damage. To address this question, we generated cellular knockout models of FA core complex components and FANCD2 and found that FANCD2-null mutants display higher levels of spontaneous chromosomal damage and hypersensitivity to replication-blocking lesions than Fanconi anemia complementation group L (FANCL)-null mutants, suggesting that FANCD2 provides a basal level of DNA protection countering endogenous lesions in the absence of monoubiquitination...
October 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28968219/site-specific-monoubiquitination-downregulates-rab5-by-disrupting-effector-binding-and-guanine-nucleotide-conversion
#18
Donghyuk Shin, Wooju Na, Ji-Hyung Lee, Gyuhee Kim, Jiseok Baek, Seok Hee Park, Cheol Yong Choi, Sangho Lee
Rab GTPases, which are involved in intracellular trafficking pathways, have recently been reported to be ubiquitinated. However, the functions of ubiquitinated Rab proteins remain unexplored. Here we show that Rab5 is monoubiquitinated on K116, K140, and K165. Upon co-transfection with ubiquitin, Rab5 exhibited abnormalities in endosomal localization and EGF-induced EGF receptor degradation. Rab5 K140R and K165R mutants restored these abnormalities, whereas K116R did not. We derived structural models of individual monoubiquitinated Rab5 proteins (mUbRab5s) by solution scattering and observed different conformational flexibilities in a site-specific manner...
October 2, 2017: ELife
https://www.readbyqxmd.com/read/28947091/the-ubiquitin-code-in-the-ubiquitin-proteasome-system-and-autophagy
#19
REVIEW
Yong Tae Kwon, Aaron Ciechanover
The conjugation of the 76 amino acid protein ubiquitin to other proteins can alter the metabolic stability or non-proteolytic functions of the substrate. Once attached to a substrate (monoubiquitination), ubiquitin can itself be ubiquitinated on any of its seven lysine (Lys) residues or its N-terminal methionine (Met1). A single ubiquitin polymer may contain mixed linkages and/or two or more branches. In addition, ubiquitin can be conjugated with ubiquitin-like modifiers such as SUMO or small molecules such as phosphate...
November 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28946194/esculetin-ameliorates-vascular-perturbation-by-intervening-in-the-occupancy-of-h2bk120ub-at-at1-at2-tgf%C3%AE-1-and-mcp1-promoter-gene-in-thoracic-aorta-of-ir-and-t2d-rats
#20
Almesh Kadakol, Santosh Kumar Goru, Vajir Malek, Anil Bhanudas Gaikwad
Micro and macro vascular complications under diabetic condition are the responses to pathological stimuli exerted by up regulated renin angiotensin system (RAS) via deteriorating vascular physiology. Up-regulated RAS could influence in the adaptive mechanisms of target tissues to alter the abundance of angiotensin II type 1 receptor (AT1) and angiotensin II type 2 receptor (AT2). Such differential regulation of AT1 and AT2 have been reported to be associated with post-translational histone modifications (PTHMs)...
November 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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