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Monoubiquitination

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https://www.readbyqxmd.com/read/29765032/pcgf5-is-required-for-neural-differentiation-of-embryonic-stem-cells
#1
Mingze Yao, Xueke Zhou, Jiajian Zhou, Shixin Gong, Gongcheng Hu, Jiao Li, Kaimeng Huang, Ping Lai, Guang Shi, Andrew P Hutchins, Hao Sun, Huating Wang, Hongjie Yao
Polycomb repressive complex 1 (PRC1) is an important regulator of gene expression and development. PRC1 contains the E3 ligases RING1A/B, which monoubiquitinate lysine 119 at histone H2A (H2AK119ub1), and has been sub-classified into six major complexes based on the presence of a PCGF subunit. Here, we report that PCGF5, one of six PCGF paralogs, is an important requirement in the differentiation of mouse embryonic stem cells (mESCs) towards a neural cell fate. Although PCGF5 is not required for mESC self-renewal, its loss blocks mESC neural differentiation by activating the SMAD2/TGF-β signaling pathway...
May 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29760876/rinck-mediated-monoubiquitination-of-cgas-promotes-antiviral-innate-immune-responses
#2
Zhao-Shan Liu, Zi-Yu Zhang, Hong Cai, Ming Zhao, Jie Mao, Jiang Dai, Tian Xia, Xue-Min Zhang, Tao Li
Background: As an important danger signal, the presence of DNA in cytoplasm triggers potent immune responses. Cyclic GMP-AMP synthase (cGAS) is a recently characterized key sensor for cytoplasmic DNA. The engagement of cGAS with DNA leads to the synthesis of a second messenger, cyclic GMP-AMP (cGAMP), which binds and activates the downstream adaptor protein STING to promote type I interferon production. Although cGAS has been shown to play a pivotal role in innate immunity, the exact regulation of cGAS activation is not fully understood...
2018: Cell & Bioscience
https://www.readbyqxmd.com/read/29720480/targeting-usp22-suppresses-tumorigenicity-and-enhances-cisplatin-sensitivity-through-aldh1a3-downregulation-in-cancer-initiating-cells-from-lung-adenocarcinoma
#3
Xinwei Yun, Keqiang Zhang, Jinhui Wang, Rajendra P Pangeni, Lu Yang, Melissa Bonner, Jun Wu, Jami Wang, Isaac K Nardi, Ming Gao, Dan J Raz
Loss of monoubiquitination of histone H2B (H2Bub1) was found to be associated with poor-differentiation and enhanced malignancy of lung adenocarcinoma. This study, investigated the association and impact of the ubiquitin specific peptidase 22 (USP22), an H2Bub1 deubiquitinase, on stem cell-like characteristics and cisplatin resistance in cancer-initiating cells (CICs) from primary lung adenocarcinoma. CICs were isolated, enriched, and characterized from patient-derived cancer tissues using both in vitro tumorsphere formation and in vivo xenograft assays...
May 2, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29698671/a-fluorescence-polarization-based-competition-assay-for-measuring-interactions-between-unlabeled-ubiquitin-chains-and-uch37%C3%A2-rpn13
#4
Jiale Du, Eric R Strieter
Ubiquitin chains regulate distinct signaling events through cooperative interactions with effector proteins and deubiquitinases. Measuring the strength of these interactions is often challenging; either large amounts of material are required or one of the binding partners must be labeled for detection. We sought to develop a label-free method for measuring binding of ubiquitin chains to the proteasome-associated deubiquitinase UCH37 and its binding partner RPN13. The method we describe here is based on a fluorescence polarization competition (FPcomp ) assay in which fluorescent monoubiquitin is competed off the UCH37•RPN13 complex by the addition of an unlabeled ubiquitin chains...
April 23, 2018: Analytical Biochemistry
https://www.readbyqxmd.com/read/29678905/phosphorylation-of-xiap-at-threonine-180-controls-its-activity-in-wnt-signaling
#5
Victoria H Ng, Brian I Hang, Leah M Sawyer, Leif R Neitzel, Emily E Crispi, Kristie L Rose, Tessa M Popay, Alison Zhong, Laura A Lee, William P Tansey, Stacey Huppert, Ethan Lee
X-linked Inhibitor of Apoptosis (XIAP) plays an important role in preventing apoptotic cell death. XIAP has been shown to participate in signaling pathways, including Wnt signaling. XIAP regulates Wnt signaling by promoting the monoubiquitination of the co-repressor Groucho/TLE, decreasing its affinity for TCF/Lef and allowing assembly of transcriptionally active β-catenin-TCF/Lef complexes. We now demonstrate that XIAP is phosphorylated by GSK3 at threonine 180 and that an alanine mutant (XIAPT180A ) exhibits decreased Wnt activity compared to wild-type XIAP in cultured human cells and in Xenopus embryos...
April 20, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29678836/tumor-suppressor-bap1-is-essential-for-thymic-development-and-proliferative-responses-of-t-lymphocytes
#6
Teresita L Arenzana, Steve Lianoglou, Akiko Seki, Celine Eidenschenk, Tommy Cheung, Dhaya Seshasayee, Thijs Hagenbeek, Arivazhagan Sambandam, Rajkumar Noubade, Ivan Peng, Justin Lesch, Jason DeVoss, Xiumin Wu, Wyne P Lee, Patrick Caplazi, Joshua Webster, Jinfeng Liu, Victoria C Pham, David Arnott, Jennie R Lill, Zora Modrusan, Anwesha Dey, Sascha Rutz
Loss of function of the nuclear deubiquitinating enzyme BRCA1-associated protein-1 (BAP1) is associated with a wide spectrum of cancers. We report that tamoxifen-induced BAP1 deletion in adult mice resulted in severe thymic atrophy. BAP1 was critical for T cell development at several stages. In the thymus, BAP1 was required for progression through the pre-T cell receptor checkpoint. Peripheral T cells lacking BAP1 demonstrated a defect in homeostatic and antigen-driven expansion. Deletion of BAP1 resulted in suppression of E2F target genes and defects in cell cycle progression, which was dependent on the catalytic activity of BAP1, but did not require its interaction with host cell factor-1 (HCF-1)...
April 20, 2018: Science Immunology
https://www.readbyqxmd.com/read/29656179/novel-reno-protective-mechanism-of-aspirin-involves-h2ak119-monoubiquitination-and-set7-in-preventing-type-1-diabetic-nephropathy
#7
Santosh Kumar Goru, Anil Bhanudas Gaikwad
BACKGROUND: Even after several novel therapeutic approaches, the number of people with diabetic nephropathy (DN) still continues to increase globally, this suggest to find novel therapeutic strategies to prevent it completely. Recent reports, are indicating the ubiquitin proteasome system alterations in DN. Recently, we also showed that, histone H2AK119 mono-ubiquitination (H2AK119-Ub) found to regulate Set7, a key epigenetic enzyme in the development of renal fibrosis under type 1 diabetic condition...
December 2, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29629558/%C3%AE-catenin-increases-the-stability-of-egfr-by-decreasing-c-cbl-interaction-and-enhances-egfr-erk1-2-signaling-in-prostate-cancer
#8
Nensi Shrestha, Hridaya Shrestha, Taeyong Ryu, Hangun Kim, Shishli Simkhada, Young-Chang Cho, So-Yeon Park, Sayeon Cho, Kwang-Youl Lee, Jae-Hyuk Lee, Kwonseop Kim
δ-Catenin, a member of the p120-catenin subfamily of armadillo proteins, reportedly increases during the late stage of prostate cancer. Our previous study demonstrates that δ- catenin increases the stability of EGFR in prostate cancer cell lines. However, the molecular mechanism behind δ-cateninmediated enhanced stability of EGFR was not explored. In this study, we hypothesized that δ-catenin enhances the protein stability of EGFR by inhibiting its lysosomal degradation that is mediated by c-casitas b-lineage lymphoma (c-Cbl), a RING domain E3 ligase...
April 5, 2018: Molecules and Cells
https://www.readbyqxmd.com/read/29626091/the-ubiquitin-specific-protease-usp8-deubiquitinates-and-stabilizes-cx43
#9
Jian Sun, Qianwen Hu, Hong Peng, Cheng Peng, Liheng Zhou, Jinsong Lu, Chuanxin Huang
Connexin 43 (Cx43, also known as GJA1), is the most ubiquitously expressed connexin isoform in mammalian tissues. It forms intercellular gap junction (GJ) channels, enabling adjacent cells to communicate both electrically and metabolically. Cx43 is a short-lived protein which can be quickly degraded by the ubiquitin-dependent proteasomal, endolysosomal and autophagosomal pathways. Here, we report that the ubiquitin-specific peptidase 8 (USP8) interacts with and deubiquitinates Cx43. USP8 reduces both multiple monoubiquitination and polyubiquitination of Cx43 to prevent autophagy-mediated degradation...
April 6, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29605812/targeted-mass-spectrometry-enables-robust-quantification-of-fancd2-mono-ubiquitination-in-response-to-dna-damage
#10
Jeffrey R Whiteaker, Lei Zhao, Richard G Ivey, Marilyn Sanchez-Bonilla, Heather D Moore, Regine M Schoenherr, Ping Yan, Chenwei Lin, Akiko Shimamura, Amanda G Paulovich
The Fanconi anemia pathway is an important coordinator of DNA repair pathways and is particularly relevant to repair of DNA inter-strand crosslinks. Central to the pathway is monoubiquitination of FANCD2, requiring the function of multiple proteins in an upstream Fanconi core complex. We present development and analytical characterization of a novel assay for quantification of unmodified and monoubiquitinated FANCD2 proteoforms, based on peptide immunoaffinity enrichment and targeted multiple reaction monitoring mass spectrometry (immuno-MRM)...
March 21, 2018: DNA Repair
https://www.readbyqxmd.com/read/29598900/small-molecules-that-bind-to-the-ubiquitin-binding-motif-of-rev1-inhibit-rev1-interaction-with-k164-monoubiquitinated-pcna-and-suppress-dna-damage-tolerance
#11
Murugendra Vanarotti, Benjamin J Evison, Marcelo L Actis, Akira Inoue, Ezelle T McDonald, Youming Shao, Richard J Heath, Naoaki Fujii
REV1 protein is a mutagenic DNA damage tolerance (DDT) mediator and encodes two ubiquitin-binding motifs (i.e., UBM1 and UBM2) that are essential for the DDT function. REV1 interacts with K164-monoubiquitinated PCNA (UbPCNA) in cells upon DNA-damaging stress. By using AlphaScreen assays to detect inhibition of REV1 and UbPCNA protein interactions along with an NMR-based strategy, we identified small-molecule compounds that inhibit the REV1/UbPCNA interaction and that directly bind to REV1 UBM2. In cells, one of the compound prevented recruitment of REV1 to PCNA foci on chromatin upon cisplatin treatment, delayed removal of UV-induced cyclopyrimidine dimers from nuclei, prevented UV-induced mutation of HPRT gene, and diminished clonogenic survival of cells that were challenged by cyclophosphamide or cisplatin...
March 19, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29590477/rna-splicing-factor-sart3-regulates-translesion-dna-synthesis
#12
Min Huang, Bo Zhou, Juanjuan Gong, Lingyu Xing, Xiaolu Ma, Fengli Wang, Wei Wu, Hongyan Shen, Chenyi Sun, Xuefei Zhu, Yeran Yang, Yazhou Sun, Yang Liu, Tie-Shan Tang, Caixia Guo
Translesion DNA synthesis (TLS) is one mode of DNA damage tolerance that uses specialized DNA polymerases to replicate damaged DNA. DNA polymerase η (Polη) is well known to facilitate TLS across ultraviolet (UV) irradiation and mutations in POLH are implicated in skin carcinogenesis. However, the basis for recruitment of Polη to stalled replication forks is not completely understood. In this study, we used an affinity purification approach to isolate a Polη-containing complex and have identified SART3, a pre-mRNA splicing factor, as a critical regulator to modulate the recruitment of Polη and its partner RAD18 after UV exposure...
March 24, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29507117/crl7-smu1-e3-ligase-complex-driven-h2b-ubiquitylation-functions-in-sister-chromatid-cohesion-by-regulating-smc1-expression
#13
Varun Jayeshkumar Shah, Subbareddy Maddika
Cullin-RING-type E3 ligases (CRLs) control a broad range of biological processes by ubiquitylating numerous cellular substrates. However, the role of CRL E3 ligases in chromatid cohesion is unknown. In this study, we identified a new CRL-type E3 ligase (designated as CRL7SMU1 complex) that has an essential role in the maintenance of chromatid cohesion. We demonstrate that SMU1, DDB1, CUL7 and RNF40 are integral components of this complex. SMU1, by acting as a substrate recognition module, binds to H2B and mediates monoubiquitylation at the lysine (K) residue K120 through CRL7SMU1 E3 ligase complex...
April 26, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29462142/rnf8-and-scml2-cooperate-to-regulate-ubiquitination-and-h3k27-acetylation-for-escape-gene-activation-on-the-sex-chromosomes
#14
Shannel R Adams, So Maezawa, Kris G Alavattam, Hironori Abe, Akihiko Sakashita, Megan Shroder, Tyler J Broering, Julie Sroga Rios, Michael A Thomas, Xinhua Lin, Carolyn M Price, Artem Barski, Paul R Andreassen, Satoshi H Namekawa
The sex chromosomes are enriched with germline genes that are activated during the late stages of spermatogenesis. Due to meiotic sex chromosome inactivation (MSCI), these sex chromosome-linked genes must escape silencing for activation in spermatids, thereby ensuring their functions for male reproduction. RNF8, a DNA damage response protein, and SCML2, a germline-specific Polycomb protein, are two major, known regulators of this process. Here, we show that RNF8 and SCML2 cooperate to regulate ubiquitination during meiosis, an early step to establish active histone modifications for subsequent gene activation...
February 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29426904/trim56-mediated-monoubiquitination-of-cgas-for-cytosolic-dna-sensing
#15
Gil Ju Seo, Charlotte Kim, Woo-Jin Shin, Ella H Sklan, Hyungjin Eoh, Jae U Jung
Intracellular nucleic acid sensors often undergo sophisticated modifications that are critical for the regulation of antimicrobial responses. Upon recognition of DNA, the cytosolic sensor cyclic GMP-AMP (cGAMP) synthase (cGAS) produces the second messenger cGAMP, which subsequently initiates downstream signaling to induce interferon-αβ (IFNαβ) production. Here we report that TRIM56 E3 ligase-induced monoubiquitination of cGAS is important for cytosolic DNA sensing and IFNαβ production to induce anti-DNA viral immunity...
February 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29415948/effect-of-gestational-cadmium-exposure-on-fetal-growth-polyubiquitinated-protein-and-monoubiqutin-levels-in-the-fetal-liver-of-mice
#16
Hisaka Kurita, Tatsuya Hasegawa, Yoshiyuki Seko, Hisamitsu Nagase, Maki Tokumoto, Jin-Yong Lee, Masahiko Satoh
Cadmium (Cd) is an environmental pollutant present in contaminated water, food and soil. Cd adversely affects fetal development. We exposed pregnant mice to daily oral doses of 5 and 10 mg/kg Cd and examined fetal growth. It was demonstrated that the exposure to Cd (10 mg/kg) during gestation caused fetal growth retardation (FGR). Investigation of the ubiquitin-proteasome system in fetal livers of mice exposed to gestational Cd revealed increased polyubiquitinated protein accumulation, contrasting with decreased levels of monoubiquitin protein...
2018: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/29400315/the-pex4p-pex22p-complex-from-hansenula-polymorpha-biophysical-analysis-crystallization-and-x-ray-diffraction-characterization
#17
Ameena M Ali, Jack Atmaj, Alaa Adawy, Sergey Lunev, Niels Van Oosterwijk, Sun Rei Yan, Chris Williams, Matthew R Groves
Peroxisomes are a major cellular compartment of eukaryotic cells, and are involved in a variety of metabolic functions and pathways according to species, cell type and environmental conditions. Their biogenesis relies on conserved genes known as PEX genes that encode peroxin proteins. Peroxisomal membrane proteins and peroxisomal matrix proteins are generated in the cytosol and are subsequently imported into the peroxisome post-translationally. Matrix proteins containing a peroxisomal targeting signal type 1 (PTS1) are recognized by the cycling receptor Pex5p and transported to the peroxisomal lumen...
February 1, 2018: Acta Crystallographica. Section F, Structural Biology Communications
https://www.readbyqxmd.com/read/29394375/replication-stress-induces-accumulation-of-fancd2-at-central-region-of-large-fragile-genes
#18
Yusuke Okamoto, Watal M Iwasaki, Kazuto Kugou, Kazuki K Takahashi, Arisa Oda, Koichi Sato, Wataru Kobayashi, Hidehiko Kawai, Ryo Sakasai, Akifumi Takaori-Kondo, Takashi Yamamoto, Masato T Kanemaki, Masato Taoka, Toshiaki Isobe, Hitoshi Kurumizaka, Hideki Innan, Kunihiro Ohta, Masamichi Ishiai, Minoru Takata
During mild replication stress provoked by low dose aphidicolin (APH) treatment, the key Fanconi anemia protein FANCD2 accumulates on common fragile sites, observed as sister foci, and protects genome stability. To gain further insights into FANCD2 function and its regulatory mechanisms, we examined the genome-wide chromatin localization of FANCD2 in this setting by ChIP-seq analysis. We found that FANCD2 mostly accumulates in the central regions of a set of large transcribed genes that were extensively overlapped with known CFS...
April 6, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29352077/whole-genome-sequencing-of-suppressor-dna-mixtures-identifies-pathways-that-compensate-for-chromosome-segregation-defects-in-schizosaccharomyces-pombe
#19
Xingya Xu, Li Wang, Mitsuhiro Yanagida
Suppressor screening is a powerful method to identify genes that, when mutated, rescue the temperature sensitivity of the original mutation. Previously, however, identification of suppressor mutations has been technically difficult. Due to the small genome size of Schizosaccharomyces pombe , we developed a spontaneous suppressor screening technique, followed by a cost-effective sequencing method. Genomic DNAs of 10 revertants that survived at the restrictive temperature of the original temperature sensitive (ts) mutant were mixed together as one sample before constructing a library for sequencing...
March 2, 2018: G3: Genes—Genomes—Genetics
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
#20
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
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