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https://www.readbyqxmd.com/read/28088103/chemically-enzymatic-synthesis-of-photosensitive-dna
#1
Kinga Westphal, Magdalena Zdrowowicz, Agnieszka Zylicz-Stachula, Janusz Rak
The sensitizing propensity of radio-/photosensitizing nucleoside depends on DNA sequence surrounding a sensitizer. Therefore, in order to compare sensitizers with regard to their ability to induce a DNA damage one has to study the sequence dependence of damage yield. However, chemical synthesis of oligonucleotides labeled with sensitizing nucleosides is hindered due to the fact that a limited number of such nucleoside phosphoramidites are accessible. Here, we report on a chemically-enzymatic method, employing a DNA polymerase and ligase, that enables a modified nucleoside, in the form of its 5'-triphosphate, to be incorporated into DNA fragment in a pre-determined site...
January 5, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28087809/trim13-potentiates-tlr2-mediated-nf-%C3%AE%C2%BAb-activation-via-k29-linked-polyubiquitination-of-traf6
#2
Bin Huang, Suk-Hwan Baek
Ubiquitination is a versatile post-translational modification involved in NF-κB activation of TLR signaling. Here, we demonstrated that Trim13, an E3 ubiquitin ligase, is up-regulated in macrophages upon stimulation with TLR2 ligand. Knock-down of Trim13 attenuated TLR2-mediated production of cytokines/chemokines and formation of foam cells, as well as activation of NF-κB. Trim13 interacts with TRAF6 and potentiates NF-κB activity via ubiquitination of TRAF6. Overexpression of inactive mutant (C10/13A) or RING deletion mutant of Trim13 did not potentiate ubiquitination of TRAF6 or activation of NF-κB...
January 13, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28087701/the-ubiquitin-ligase-nedd4l-regulates-the-na-k-2cl-co-transporter-nkcc1-slc12a2-in-the-colon
#3
Chong Jiang, Hiroshi Kawabe, Daniela Rotin
The ubiquitin ligase Nedd4-like (Nedd4L, or Nedd4-2) binds to and regulates stability of the epithelial Na+ channel (ENaC) in salt absorbing epithelia in the kidney, lung, and other tissues. Its role in the distal colon, which also absorbs salt and fluid and expresses ENaC, is unknown. Using conditional knockout approach to knockout Nedd4L in mice intestinal epithelium (Nedd4Lf/f;Vil-CreERT2) we show here that Nedd4L depletion leads to a higher steady-state short circuit current (Isc) in mouse distal colon tissue relative to controls...
January 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28087699/activation-of-c-abl-kinase-potentiates-the-anti-myeloma-drug-lenalidomide-by-promoting-dda1-recruitment-to-the-crl4-ubiquitin-ligase
#4
Shaobing Gao, Chenlu Geng, Tianyu Song, Xuanru Lin, Jiye Liu, Zhen Cai, Yong Cang
Cullin Ring Ligase 4 (CRL4), a complex of Cul4 and DDB1, regulates cell cycle, DNA damage repair, and chromatin replication by targeting a variety of substrates for ubiquitination. CRL4 is also hijacked by viral proteins or thalidomide-derived compounds to degrade host restriction factors. Here we report that the c-Abl non-receptor kinase phosphorylates DDB1 at residue Y316 to recruit a small regulatory protein DDA1, leading to increased substrate ubiquitination. Pharmacological inhibition or genetic ablation of the Abl-DDB1-DDA1 axis decreases the ubiquitination of CRL4 substrates, including IKZF1 and IKZF3 in lenalidomide-treated multiple myeloma cells...
January 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28087580/self-regulating-ubiquitin-ligases
#5
Spencer Hill, Gary Kleiger
No abstract text is available yet for this article.
January 13, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28087428/polycomb-complexes-prc1-and-their-function-in-hematopoiesis
#6
REVIEW
Miguel Vidal, Katharzina Starowicz
Hematopoiesis, the process by which blood cells are continuously produced, is one of the best studied differentiation pathways. Hematological diseases are associated to reiterated mutations in genes encoding important gene expression regulators, including chromatin regulators. Among them, the Polycomb group (PcG) of proteins is an essential system of gene silencing involved in the maintenance of cell identities during differentiation. PcG proteins assemble into two major types of Polycomb repressive complexes (PRC) endowed with distinct histone tail modifying activities...
January 10, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28081275/role-of-xrcc1-gene-polymorphisms-in-non-small-cell-lung-cancer-cisplatin-based-chemotherapy-and-their-effect-on-clinical-and-pathological-characteristics
#7
H F Liu, J S Liu, J H Deng, R R Wu
Non-small cell lung cancer (NSCLC) is the most common cancer globally. The XRCC1 protein interacts with ligase and poly(ADP-ribose) polymerase to repair cisplatin-induced DNA damage. The authors of previous studies have reported XRCC1 Arg399Gln, Arg280His, and Arg194Trp polymorphisms and advanced NSCLC prognosis, but the results are inconclusive. We investigated the association between clinical outcome and XRCC1 Arg399Gln, Arg280His, and Arg194Trp polymorphisms in advanced NSCLC patients treated with cisplatin...
December 23, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28079882/stability-of-the-cancer-target-ddias-is-regulated-by-the-chip-hsp70-pathway-in-lung-cancer-cells
#8
Kyoung-Jae Won, Joo-Young Im, Bo-Kyung Kim, Hyun Seung Ban, Young-Jin Jung, Kyeong Eun Jung, Misun Won
DNA damage-induced apoptosis suppressor (DDIAS) rescues lung cancer cells from apoptosis in response to DNA damage. DDIAS is transcriptionally activated by NFATc1 and EGF-mediated ERK5/MEF2B, leading to cisplatin resistance and cell invasion. Therefore, DDIAS is suggested as a therapeutic target for lung cancer. Here, we report that DDIAS stability is regulated by E3 U-box ubiquitin ligase carboxyl terminus of HSP70-interacting protein (CHIP)-mediated proteasomal degradation. We first isolated CHIP as an interacting partner of DDIAS by yeast two-hybrid screening...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28077643/efficient-vpu-mediated-tetherin-antagonism-by-an-hiv-1-group-o-strain
#9
Katharina Mack, Kathrin Starz, Daniel Sauter, Simon Langer, Frederic Bibollet-Ruche, Gerald H Learn, Christina M Stürzel, Marie Leoz, Jean-Christophe Plantier, Matthias Geyer, Beatrice H Hahn, Frank Kirchhoff
: Simian immunodeficiency viruses (SIVs) use their Nef proteins to counteract the restriction factor tetherin. However, a deletion in human tetherin prevents antagonism by the Nef proteins of SIVcpz and SIVgor, which represent the ape precursors of human immunodeficiency virus type 1 (HIV-1). To promote virus release from infected cells, pandemic HIV-1 group M strains evolved Vpu as tetherin antagonist, while the Nef protein of less widespread HIV-1 group O strains acquired the ability to target a region adjacent to this deletion...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077445/human-antiviral-protein-ifix-suppresses-viral-gene-expression-during-hsv-1-infection-and-is-counteracted-by-virus-induced-proteasomal-degradation
#10
Marni S Crow, Ileana M Cristea
The interferon inducible protein X (IFIX), a member of the PYHIN family, was recently recognized as an antiviral factor against infection with herpes simplex virus 1 (HSV-1). IFIX binds viral DNA upon infection and promotes antiviral cytokines expression. How IFIX exerts its host defense functions and whether it is inhibited by the virus remains unknown. Here, we integrated live cell microscopy, proteomics, IFIX domain characterization, and molecular virology to investigate IFIX regulation and antiviral functions during HSV-1 infection...
January 11, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28077082/the-arabidopsis-paralogs-pub46-and-pub48-encoding-u-box-e3-ubiquitin-ligases-are-essential-for-plant-response-to-drought-stress
#11
Guy Adler, Zvia Konrad, Lyad Zamir, Amit Kumar Mishra, Dina Raveh, Dudy Bar-Zvi
BACKGROUND: Plants respond to abiotic stress on physiological, biochemical and molecular levels. This includes a global change in their cellular proteome achieved by changes in the pattern of their protein synthesis and degradation. The ubiquitin-proteasome system (UPS) is a key player in protein degradation in eukaryotes. Proteins are marked for degradation by the proteasome by coupling short chains of ubiquitin polypeptides in a three-step pathway. The last and regulatory stage is catalyzed by a member of a large family of substrate-specific ubiquitin ligases...
January 11, 2017: BMC Plant Biology
https://www.readbyqxmd.com/read/28076680/regulating-the-master-regulator-controlling-ubiquitination-by-thinking-outside-the-active-site
#12
Stacey-Lynn Paiva, Sara R da Silva, Elvin D de Araujo, Patrick Thomas Gunning
The labeling of proteins with ubiquitin/ubiquitin-like (Ubl) proteins is crucial for several physiological processes and in the onset of various diseases. Recently, targeting ubiquitin protein labeling has shifted towards the use of allosteric mechanisms over classical activity-based approaches. Allosteric enzyme regulation offers the potential for greater selectivity and has demonstrated less susceptibility to acquired resistance often associated with active site inhibitors. Furthermore, the isoform diversity among E1 activating, E2 conjugating, E3 ligase and deubiquitinating (DUB) enzymes offers an ideal platform for modulating activity via allostery...
January 11, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28074012/reduced-abundance-of-the-e3-ubiquitin-ligase-e6ap-contributes-to-decreased-expression-of-the-ink4-arf-locus-in-non-small-cell-lung-cancer
#13
Cristina Gamell, Twishi Gulati, Yaara Levav-Cohen, Richard J Young, Hongdo Do, Pat Pilling, Elena Takano, Neil Watkins, Stephen B Fox, Prudence Russell, Doron Ginsberg, Brendon J Monahan, Gavin Wright, Alex Dobrovic, Sue Haupt, Ben Solomon, Ygal Haupt
The tumor suppressor p16(INK4a), one protein encoded by the INK4/ARF locus, is frequently absent in multiple cancers, including non-small cell lung cancer (NSCLC). Whereas increased methylation of the encoding gene (CDKN2A) accounts for its loss in a third of patients, no molecular explanation exists for the remainder. We unraveled an alternative mechanism for the silencing of the INK4/ARF locus involving the E3 ubiquitin ligase and transcriptional cofactor E6AP (also known as UBE3A). We found that the expression of three tumor suppressor genes encoded in the INK4/ARF locus (p15(INK4b), p16(INK4a), and p19(ARF)) was decreased in E6AP(-/-) mouse embryo fibroblasts...
January 10, 2017: Science Signaling
https://www.readbyqxmd.com/read/28073917/the-e3-ubiquitin-ligase-rnf114-and-tab1-degradation-are-required-for-maternal-to-zygotic-transition
#14
Ye Yang, Cheng Zhou, Ying Wang, Weixiao Liu, Chao Liu, Liying Wang, Yujiao Liu, Yongliang Shang, Mingrui Li, Shuai Zhou, Yuanting Wang, Wentao Zeng, Jianli Zhou, Ran Huo, Wei Li
The functional role of the ubiquitin-proteasome pathway during maternal-to-zygotic transition (MZT) remains to be elucidated. Here we show that the E3 ubiquitin ligase, Rnf114, is highly expressed in mouse oocytes and that knockdown of Rnf114 inhibits development beyond the two-cell stage. To study the underlying mechanism, we identify its candidate substrates using a 9,000-protein microarray and validate them using an in vitro ubiquitination system. We show that five substrates could be degraded by RNF114-mediated ubiquitination, including TAB1...
January 10, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28073915/ube2e1-ubch6-is-a-critical-in-vivo-e2-for-the-prc1-catalyzed-ubiquitination-of-h2a-at-k119
#15
Keith Wheaton, Feroz Sarkari, Beena Stanly Johns, Hossein Davarinejad, Olga Egorova, Lilia Kaustov, Brian Raught, Vivian Saridakis, Yi Sheng
UbE2E1/UbcH6 is an E2 ubiquitin conjugating enzyme that is regulated by USP7. We identified UbE2E1 as a novel component of Polycomb Repressive Complex 1 (PRC1), the E3 ligase complex responsible for histone H2A ubiquitination and gene silencing. We demonstrate that UbE2E1 is critical for the mono-ubiquitination of H2A at residue K119 (uH2AK119) through its association with the PRC1 complex. UbE2E1 interacts with PRC1 subunits including Ring1A and Ring1B. Overexpression of UbE2E1 results in increased levels of uH2AK119 whereas overexpression of catalytically inactive UbE2E1C131A or UbE2E1 knockdown results in decreased levels of uH2AK119...
January 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28073378/hectd1-controls-the-protein-level-of-iqgap1-to-regulate-the-dynamics-of-adhesive-structures
#16
Xiaoli Shen, Zanhui Jia, Donato D'Alonzo, Xinggang Wang, Elisabeth Bruder, Fabienne Hélène Emch, Christian De Geyter, Hong Zhang
BACKGROUND: Cell migration including collective cell movement and individual cell migration are crucial factors in embryogenesis. During the spreading/migration of cells, several types of adhesive structures physically interacting with the extracellular matrix (ECM) or with another cell have been described and the formation and maturation of adhesion structures are coordinated, however the molecular pathways involved are still not fully understood. RESULTS: We generated a mouse embryonic fibroblast line (MEF) from homozygous mutant (Hectd1 (R/R) , Hectd1 (Gt(RRC200)) ) mouse of the E3 ubiquitin ligase for inhibin B receptor (Hectd1)...
January 5, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28072566/guard-the-guardian-a-crl4-ligase-stands-watch-over-histone-production
#17
Fabienne Lampert, Mia M L Brodersen, Matthias Peter
Histones are evolutionarily conserved proteins that together with DNA constitute eukaryotic chromatin in a defined stoichiometry. Core histones are dynamic scaffolding proteins that undergo a myriad of post-translational modifications, which selectively engage chromosome condensation, replication, transcription and DNA damage repair. Cullin4-RING ubiquitin E3 ligases are known to hold pivotal roles in a wide spectrum of chromatin biology ranging from chromatin remodeling and transcriptional repression, to sensing of cytotoxic DNA lesions...
January 10, 2017: Nucleus
https://www.readbyqxmd.com/read/28070834/resveratrol-modulates-gsh-system-in-c6-astroglial-cells-through-heme-oxygenase-1-pathway
#18
Bernardo Assein Arús, Débora Guerini Souza, Bruna Bellaver, Diogo Onofre Souza, Carlos-Alberto Gonçalves, André Quincozes-Santos, Larissa Daniele Bobermin
Resveratrol is a dietary polyphenol that displays neuroprotective properties in several in vivo and in vitro experimental models, by modulating oxidative and inflammatory responses. Glutathione (GSH) is a key antioxidant in the central nervous system (CNS) that modulates several cellular processes, and its depletion is associated with oxidative stress and inflammation. Therefore, this study sought to investigate the protective effects of resveratrol against GSH depletion pharmacologically induced by buthionine sulfoximine (BSO) in C6 astroglial cells, as well as its underlying cellular mechanisms...
January 9, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28069866/trim-proteins-and-diseases
#19
REVIEW
Masashi Watanabe, Shigetsugu Hatakeyama
Ubiquitination is one of the posttranslational modifications that regulates a number of intracellular events including signal transduction, protein quality control, transcription, cell cycle, apoptosis and development. The ubiquitin system functions as a garbage machine to degrade target proteins and as a regulator for several signalling pathways. Biochemical reaction of ubiquitination requires several enzymes including E1, E2 and E3, and E3 ubiquitin ligases play roles as receptors for recognizing target proteins...
January 7, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28069818/ssek1-and-ssek3-t3ss-effectors-inhibit-nf-%C3%AE%C2%BAb-signalling-and-necroptotic-cell-death-in-salmonella-infected-macrophages
#20
Regina A Günster, Sophie A Matthews, David W Holden, Teresa L M Thurston
Within host cells such as macrophages, Salmonella enterica translocates virulence (effector) proteins across its vacuolar membrane using the SPI-2 type III secretion system. Previously it has been shown that when expressed ectopically the effectors SseK1 and SseK3 inhibit TNFα-induced NF-κB activation. In this study we show that ectopically expressed SseK1, SseK2 and SseK3 suppressed TNFα-, but not TLR4-, or interleukin-induced NF-κB activation. Inhibition required a DXD motif, which in SseK1 and SseK3 is essential for protein Arginine-N-acetylglucosamine (GlcNAc)-ylation...
January 9, 2017: Infection and Immunity
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