127 research outputs found
The RNF168 paralog RNF169 defines a new class of ubiquitylated histone reader involved in the response to DNA damage.
Site-specific histone ubiquitylation plays a central role in orchestrating the response to DNA double-strand breaks (DSBs). DSBs elicit a cascade of events controlled by the ubiquitin ligase RNF168, which promotes the accumulation of repair factors such as 53BP1 and BRCA1 on the chromatin flanking the break site. RNF168 also promotes its own accumulation, and that of its paralog RNF169, but how they recognize ubiquitylated chromatin is unknown. Using methyl-TROSY solution NMR spectroscopy and molecular dynamics simulations, we present an atomic resolution model of human RNF169 binding to a ubiquitylated nucleosome, and validate it by electron cryomicroscopy. We establish that RNF169 binds to ubiquitylated H2A-Lys13/Lys15 in a manner that involves its canonical ubiquitin-binding helix and a pair of arginine-rich motifs that interact with the nucleosome acidic patch. This three-pronged interaction mechanism is distinct from that by which 53BP1 binds to ubiquitylated H2A-Lys15 highlighting the diversity in site-specific recognition of ubiquitylated nucleosomes
Vaccinia virus protein C16 acts intracellularly to modulate the host response and promote virulence
The vaccinia virus (VACV) strain Western Reserve C16 protein has been characterized and its effects on virus replication and virulence have been determined. The C16L gene is present in the inverted terminal repeat and so is one of the few VACV genes that are diploid. The C16 protein is highly conserved between different VACV strains, and also in the orthopoxviruses variola virus, ectromelia virus, horsepox virus and cowpox virus. C16 is a 37.5 kDa protein, which is expressed early during infection and localizes to the cell nucleus and cytoplasm of infected and transfected cells. The loss of the C16L gene had no effect on virus growth kinetics but did reduce plaque size slightly. Furthermore, the virulence of a virus lacking C16L (vΔC16) was reduced in a murine intranasal model compared with control viruses and there were reduced virus titres from 4 days post-infection. In the absence of C16, the recruitment of inflammatory cells in the lung and bronchoalveolar lavage was increased early after infection (day 3) and more CD4+ and CD8+ T cells expressed the CD69 activation marker. Conversely, late after infection with vΔC16 (day 10) there were fewer T cells remaining, indicating more rapid clearance of infection. Collectively, these data indicate that C16 diminishes the immune response and is an intracellular immunomodulator
RETRACTED ARTICLE: Mir-655 up-regulation suppresses cell invasion by targeting pituitary tumor-transforming gene-1 in esophageal squamous cell carcinoma
microRNA-30b inhibits cell invasion and migration through targeting collagen triple helix repeat containing 1 in non-small cell lung cancer
Higher visceral fat area increases the risk of vitamin D insufficiency and deficiency in Chinese adults
A conjugate of octamer-binding transcription factor 4 and toll-like receptor 7 agonist prevents the growth and metastasis of testis embryonic carcinoma
A 13C-detected 15N double-quantum NMR experiment to probe arginine side-chain guanidinium 15Nη chemical shifts
Renal interstitial fibrosis induced by high-dose mesoporous silica nanoparticles via the NF-κB signaling pathway
Xi Chen,1,2 Wang Zhouhua,1 Zhou Jie,1 Fu Xinlu,3 Liang Jinqiang,3 Qiu Yuwen,3 Huang Zhiying1,31School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Pharmaceutical Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 3Center of Laboratory Animals, Sun Yat-sen University, Guangzhou, People’s Republic of China Abstract: Previous studies have indicated that the nephrotoxicity induced by mesoporous silica nanoparticles (MSNs) is closely related to inflammation. Nuclear factor kappa B (NF-κB), a common rapid transcription factor associated with inflammation, plays an important role in the process of many kidney diseases. Acute toxicity assessment with a high-dose exposure is critical for the development of nanoparticle, as a part of standardized procedures for the evaluation of their toxicity. The present study was undertaken to observe the acute toxicity, predict the potential target organs of MSNs injury, and test the hypothesis that the NF-κB pathway plays a role in mediating the acute kidney injury and renal interstitial fibrosis in mice induced by MSNs. Balb/c mice were intraperitoneally injected with MSNs at concentrations of 150, 300, or 600 mg/kg. All of the animals were euthanized 2 and 12 days after exposure, and the blood and kidney tissues were collected for further studies. In vitro, the cytotoxicity, fibrosis markers, and NF-κB pathway were measured in a normal rat kidney cell line (NRK-52E). Acute kidney injury was induced by MSNs in mice after 2 days, some renal tubules regenerated and renal interstitial fibrosis was also observed. The expression of fibrosis markers and the nuclear translocation of NF-κB p65 in the kidney homogenates increased after exposure to MSNs. The in vitro study showed that MSNs cause cytotoxicity in NRK-52E cells and increased the expression of fibrosis markers. In addition, the NF-κB pathway could be induced, and inhibition of the NF-κB pathway could alleviate the fibrosis caused by MSNs. We conclude that inflammation is a major effector of the acute kidney toxicity induced by MSNs and results in renal interstitial fibrosis, which is mediated by the NF-κB signaling pathway.Keywords: mesoporous silica nanoparticles (MSNs), acute kidney injury, renal interstitial fibrosis, NF-κ
Synthesis and characterization of red phosphorescent-conjugated polymers containing charged iridium complexes and carbazole unit
10.1016/j.synthmet.2007.07.017Synthetic Metals15721813-822SYME
Investigations on the automatic precision polishing of curved surfaces using a five-axis machining centre
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