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https://www.readbyqxmd.com/read/28723727/longitudinal-analysis-of-motor-symptoms-and-histopathology-in-woozy-mice-a-model-of-cerebellar-ataxia
#1
Takemitsu Hayashi, Tomoya Onozato, Isao Wanajo, Morimichi Hayashi, Hiroo Takeda, Yoshikazu Fujimori
Woozy (wz) mice develop ataxia and carry a mutation in the Sil1 gene. Homozygous wz mice have been characterized histopathologically, but no details of their motor function have been reported. In the present study, to comprehensively understand the relationship between symptomatic progression and pathological feature, we evaluated motor function and neurodegeneration with age from presymptomatic to terminal stages. We evaluated the motor function of homozygous and heterozygous wz mice aged from 5 to 71 weeks...
July 18, 2017: Neuroreport
https://www.readbyqxmd.com/read/28723672/e3-ubiquitin-ligase-tripartite-motif-containing-71-promotes-the-proliferation-of-non-small-cell-lung-cancer-through-the-inhibitor-of-kappab-%C3%AE-nuclear-factor-kappab-pathway
#2
Hongjiu Ren, Yitong Xu, Qiongzi Wang, Jun Jiang, Wudumuli, Linping Hui, Qingfu Zhang, Xiupeng Zhang, Enhua Wang, Limei Sun, Xueshan Qiu
Tripartite motif-containing (TRIM) 71 belongs to the TRIM protein family. Many studies have shown that TRIM71 plays conserved roles in stem cell proliferation, differentiation, and embryonic development; however, the relationship between TRIM71 and tumorigenesis is not clear. In this study, we demonstrate that TRIM71 expression in non-small cell lung cancer (NSCLC) is associated with tumor size, lymph node metastasis, TNM stage, and poor prognosis. We found that TRIM71 was highly expressed in NSCLC cell lines compared with that in human normal bronchial epithelial cells...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723631/cbl-b-predicts-postoperative-survival-in-patients-with-resectable-pancreatic-ductal-adenocarcinoma
#3
Qian Dong, Yuteng Ma, Yao Zhang, Xiujuan Qu, Zhi Li, Yafei Qi, Yunpeng Liu, Ce Li, Kai Li, Xianghong Yang, Xiaofang Che
Casitas B-lineage lymphoma b (Cbl-b) is a ubiquitin-protein ligase and a signal transducing adaptor protein involved in immune regulation, and it may be involved in the development and progression of cancer. We investigated the association between Cbl-b expression and prognosis in patients with resectable pancreatic ductal adenocarcinoma (PDAC). The clinicopathological characteristics and survival data of 134 patients with surgery for PDAC between January 2009 and February 2012 were retrospectively evaluated, and Cbl-b expression was assayed by immunohistochemical staining...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723619/a-novel-sharpin-prmt5-h3r2me1-axis-is-essential-for-lung-cancer-cell-invasion
#4
Tingxiong Fu, Xiuwei Lv, Qingzhi Kong, Changjing Yuan
SHARPIN (Shank-associated RH domain interacting protein) is the main component of the linear ubiquitin chain activation complex (LUBAC). SHARPIN is involved in regulating inflammation and cancer progression. However, whether SHARPIN plays an important role in lung cancer metastasis and the potential underlying mechanism are still unknown. Here, for the first time, we reported that SHARPIN expression is closely related to lung cancer progression. Moreover, SHARPIN plays a central role in controlling lung cancer cell metastasis...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722725/the-monogenic-autoinflammatory-diseases-define-new-pathways-in-human-innate-immunity-and-inflammation
#5
REVIEW
Kalpana Manthiram, Qing Zhou, Ivona Aksentijevich, Daniel L Kastner
Autoinflammatory diseases were first recognized nearly 20 years ago as distinct clinical and immunological entities caused by dysregulation in the innate immune system. Since then, advances in genomic techniques have led to the identification of new monogenic disorders and their corresponding signaling pathways. Here we review these monogenic autoinflammatory diseases, ranging from periodic fever syndromes caused by dysregulated inflammasome-mediated production of the cytokine IL-1β to disorders arising from perturbations in signaling by the transcription factor NF-κB, ubiquitination, cytokine signaling, protein folding, type I interferon production and complement activation, and we further examine their molecular mechanisms...
July 19, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28722660/glypican-3-induces-oncogenicity-by-preventing-igf-1r-degradation-a-process-that-can-be-blocked-by-grb10
#6
Wei Cheng, Po-Chun Huang, Hsiao-Mei Chao, Yung-Ming Jeng, Hey-Chi Hsu, Hung-Wei Pan, Wuh-Liang Hwu, Yu-May Lee
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is a major cause of cancer-related death worldwide. Previously, we demonstrated that glypican-3 (GPC3) is highly expressed in HCC, and that GPC3 induces oncogenicity and promotes the growth of cancer cells through IGF-1 receptor (IGF-1R). In the present study, we investigated the mechanisms of GPC3-mediated enhancement of IGF-1R signaling. We demonstrated that GPC3 decreased IGF-1-induced IGF-1R ubiquitination and degradation and increased c-Myc protein levels...
July 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722511/grwd1-a-new-player-among-oncogenesis-related-ribosomal-nucleolar-proteins
#7
Takuya Takafuji, Kota Kayama, Nozomi Sugimoto, Masatoshi Fujita
Increasing attention has been paid to certain ribosomal or ribosome biosynthesis-related proteins involved in oncogenesis. Members of one group are classified as "tumor suppressive factors" represented by RPL5 and RPL11; loss of their functions leads to cancer predisposition. RPL5 and RPL11 prevent tumorigenesis by binding to and inhibiting the MDM2 ubiquitin ligase and thereby up-regulating p53. Many other candidate tumor suppressive ribosomal/nucleolar proteins have been suggested. However, it remains to be experimentally clarified whether many of these factors can actually prevent tumorigenesis and if so, how they do so...
July 19, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28722108/the-ubiquitin-ligase-scf-fbxw7%C3%AE-promotes-ata3-degradation
#8
Nan Song, Cheng Cao, Yiman Tang, Liyuan Bi, Yong Jiang, Yongsheng Zhou, Xin Song, Ling Liu, Wenshu Ge
GATA3 is a key transcription factor in cell fate determination and its dysregulation has been implicated in various types of malignancies. However, how the abundance and function of GATA3 are regulated remains unclear. Here, we report that GATA3 is physically associated with FBXW7α, and FBXW7α destabilizes GATA3 through assembly of a SKP1-CUL1-F-box E3 ligase complex. Importantly, we showed that FBXW7α promotes GATA3 ubiquitination and degradation in a GSK3 dependent manner. Furthermore, we demonstrated that FBXW7α inhibits breast cancer cells survival through destabilizing GATA3, and the expression level of FBXW7αis negatively correlated with that of GATA3 in breast cancer samples...
July 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28722047/the-effect-of-hofmeister-anions-on-water-structure-at-protein-surfaces
#9
Euihyun Lee, Jun-Ho Choi, Minhaeng Cho
To understand the effects of specific ions on protein-water interactions and the thermodynamic stability of proteins in salt solutions, we use a molecular dynamics (MD) simulation to examine the water structure, orientational distribution, and dynamics near the surface of ubiquitin. In particular, we consider NaCl, NaBF4, NaSCN, and NaClO4 salt solutions containing ubiquitin, where the anions of the latter three salts are well-known chaotropic ions in the Hofmiester anion series. The number of hydrogen bonds (H-bonds) per water molecule is found to decrease significantly at the ubiquitin-water interface, indicating a significant disruption of the water H-bonding network...
July 19, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28720849/melatonin-promotes-osteoblast-differentiation-by-regulating-osterix-protein-stability-and-expression
#10
Younho Han, Young-Mi Kim, Hyung Sik Kim, Kwang Youl Lee
Although the biological role of melatonin in osteogenic differentiation has been suggested, the mechanism of osteoblast differentiation remains unclear. Thus, the present study investigated the underlying molecular mechanisms based on osteoblast-specific transcription factors. We found that melatonin enhanced BMP-4-induced osteogenic differentiation and increased the expression of osteogenic markers, especially Osterix, which is an essential transcription factor for the differentiation of preosteoblasts into mature osteoblasts in the late stage of osteoblast differentiation...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720660/an-amish-founder-mutation-disrupts-a-pi-3-p-whamm-arp2-3-complex-driven-autophagosome-remodeling-pathway
#11
Alyssa J Mathiowetz, Emma Baple, Ashley J Russo, Alyssa M Coulter, Eric Carrano, Judith D Brown, Robert N Jinks, Andrew H Crosby, Kenneth G Campellone
Actin nucleation factors function to organize, shape, and move membrane-bound organelles, yet they remain poorly defined in relation to disease. Galloway-Mowat syndrome (GMS) is an inherited disorder characterized by microcephaly and nephrosis resulting from mutations in the WDR73 gene. This core clinical phenotype appears frequently in the Amish, where virtually all affected individuals harbor homozygous founder mutations in WDR73 as well as the closely linked WHAMM gene, which encodes a nucleation factor...
July 18, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28720576/deubiquitinating-enzyme-usp9x-suppresses-tumor-growth-via-lats-kinase-and-core-components-of-the-hippo-pathway
#12
Aleksandra Toloczko, Fusheng Guo, Hiu-Fung Yuen, Qing Wen, Stephen Andrew Wood, Yan Shan Ong, Pei Yi Chan, Asfa Alli Shaik, Jayantha Gunaratne, Mark John Dunne, Wanjin Hong, Siew Wee Chan
The core LATS kinases of the Hippo tumor suppressor pathway phosphorylate and inhibit the downstream transcriptional co-activators YAP and TAZ, which are implicated in various cancers. Recent studies have identified various E3 ubiquitin ligases that negatively regulate the Hippo pathway via ubiquitination, yet few deubiquitinating enzymes (DUB) have been implicated. In this study, we report the DUB USP9X is an important regulator of the core kinases of this pathway. USP9X interacted strongly with LATS kinase and to a lesser extent with WW45, KIBRA, and Angiomotin, and LATS co-migrated exclusively with USP9X during gel filtration chromatography analysis...
July 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28720507/formation-and-degradation-of-nitrogen-mustard-induced-mgmt-dna-crosslinking-in-16hbe-cells
#13
Jin Cheng, Feng Ye, Guorong Dan, Yuanpeng Zhao, Jiqing Zhao, Zhongmin Zou
N-methyl-2,2-di(chloroethyl)amine (HN2) is a kind of bifunctional alkyltating agent, which can react with nucleophilic groups in DNA and/or protein to form HN2-bridged crosslinking of target molecules, such as DNA-protein crosslinkings (DPC). O(6)-methylguanine-DNA methyltransferase (MGMT) is a DNA damage repair enzyme which solely repairs alkyl adduct on DNA directly. However, MGMT was detected to act as a protein cross-linked with DNA via alkylation in presence of HN2, and unexpectedly turned into a DNA damage enhancer in the form of MGMT-DNA cross-link (mDPC)...
July 15, 2017: Toxicology
https://www.readbyqxmd.com/read/28718767/in-vitro-analysis-of-rqc-activities-provides-insights-into-the-mechanism-and-function-of-cat-tailing
#14
Beatriz A Osuna, Conor J Howard, Subheksha Kc, Adam Frost, David E Weinberg
Ribosomes can stall during translation due to defects in the mRNA template or translation machinery, leading to the production of incomplete proteins. The Ribosome-associated Quality control Complex (RQC) engages stalled ribosomes and targets nascent polypeptides for proteasomal degradation. However, how each RQC component contributes to this process remains unclear. Here we demonstrate that key RQC activities-Ltn1p-dependent ubiquitination and Rqc2p-mediated Carboxy-terminal Alanine and Threonine (CAT) tail elongation-can be recapitulated in vitro with a yeast cell-free system...
July 18, 2017: ELife
https://www.readbyqxmd.com/read/28718225/proteostasis-and-ageing-insights-from-long-lived-mutant-mice
#15
William A Sands, Melissa M Page, Colin Selman
The global increase in life expectancy is creating significant medical, social and economic challenges to current and future generations. Consequently, there is a need to identify the fundamental mechanisms underlying the ageing process. This knowledge should help develop realistic interventions capable of combatting age-related disease, and thus improving late-life health and vitality. While several mechanisms have been proposed as conserved lifespan determinants, the loss of proteostasis- where proteostasis is defined here as the maintenance of the proteome- appears highly relevant to both ageing and disease...
July 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28718215/usp18-protects-against-hepatic-steatosis-and-insulin-resistance-via-its-dub-activity
#16
Shimin An, Ling-Ping Zhao, Li-Jun Shen, Siyuan Wang, Kuo Zhang, Yu Qi, Jilin Zheng, Xiao-Jing Zhang, Xue-Yong Zhu, Rong Bao, Ling Yang, Yue-Xin Lu, Zhi-Gang She, Yi-Da Tang
Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, impaired insulin sensitivity and chronic low-grade inflammation. However, the pathogenic mechanism of NAFLD is poorly understood, which hinders the exploration of possible treatments. Here, we first report that ubiquitin-specific protease 18 (USP18), a member of the deubiquitinating (DUB) enzyme family, plays regulatory roles in NAFLD progression. The expression of USP18 was down-regulated in the livers of non-alcoholic steatohepatitis (NASH) patients and high-fat diet (HFD) induced or genetically obese mice...
July 17, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28717359/the-c-terminal-effector-domain-of-non-structural-protein-1-of-influenza-a-virus-blocks-ifn-%C3%AE-production-by-targeting-tnf-receptor-associated-factor-3
#17
Wei Qian, Xiaoqin Wei, Kelei Guo, Yongtao Li, Xian Lin, Zhong Zou, Hongbo Zhou, Meilin Jin
Influenza A virus non-structural protein 1 (NS1) antagonizes interferon response through diverse strategies, particularly by inhibiting the activation of interferon regulatory factor 3 (IRF3) and IFN-β transcription. However, the underlying mechanisms used by the NS1 C-terminal effector domain (ED) to inhibit the activation of IFN-β pathway are not well understood. In this study, we used influenza virus subtype of H5N1 to demonstrate that the NS1 C-terminal ED but not the N-terminal RNA-binding domain, binds TNF receptor-associated factor 3 (TRAF3)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28717351/serial-sampling-of-serum-protein-biomarkers-for-monitoring-human-traumatic-brain-injury-dynamics-a-systematic-review
#18
REVIEW
Eric Peter Thelin, Frederick Adam Zeiler, Ari Ercole, Stefania Mondello, András Büki, Bo-Michael Bellander, Adel Helmy, David K Menon, David W Nelson
BACKGROUND: The proteins S100B, neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and neurofilament light (NF-L) have been serially sampled in serum of patients suffering from traumatic brain injury (TBI) in order to assess injury severity and tissue fate. We review the current literature of serum level dynamics of these proteins following TBI and used the term "effective half-life" (t1/2) in order to describe the "fall" rate in serum...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28716524/the-e3-ligase-hectd3-promotes-esophageal-squamous-cell-carcinoma-escc-growth-and-cell-survival-through-targeting-and-inhibiting-caspase-9-activation
#19
Yi Li, Xiaowei Wu, Lin Li, Yongshuo Liu, Chengshan Xu, Dan Su, Zhihua Liu
Apoptosis resistance is an acquired hallmark of cancer cells and many factors can contribute to the tumor cell apoptosis resistance. In this study, we demonstrated that HECTD3, overexpressed in human esophageal squamous cell carcinoma (ESCC), confers cells resistance to cisplatin-induced apoptosis and promotes cancer cell survival. HECTD3 can bind and ubiquitinate caspase-9, which leads to inhibiting caspase-9 oligomerization and association with Apaf-1, and results in suppressing caspase-9 activation and inhibiting apoptosis...
July 14, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28716105/characterization-of-four-rice-uev1-genes-required-for-lys63-linked-polyubiquitination-and-distinct-functions
#20
Qian Wang, Yuepeng Zang, Xuan Zhou, Wei Xiao
BACKGROUND: The error-free branch of the DNA-damage tolerance (DDT) pathway is orchestrated by Lys63-linked polyubiquitination of proliferating cell nuclear antigen (PCNA), and this polyubiquitination is mediated by a Ubc13-Uev complex in yeast. We have previously cloned OsUBC13 from rice, whose product functions as an E2 to promote Lys63-linked ubiquitin chain assembly in the presence of yeast or human Uev. RESULTS: Here we identify four highly conserved UEV1 genes in rice whose products are able to form stable heterodimers with OsUbc13 and mediate Lys63-linked ubiquitin chain assembly...
July 17, 2017: BMC Plant Biology
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