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Regulated Alternative Translocation

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https://www.readbyqxmd.com/read/28811582/a-new-class-of-hybrid-secretion-system-is-employed-in-pseudomonas-amyloid-biogenesis
#1
Sarah L Rouse, William J Hawthorne, Jamie-Lee Berry, Dror S Chorev, Sandra A Ionescu, Sebastian Lambert, Fisentzos Stylianou, Wiebke Ewert, Uma Mackie, R Marc L Morgan, Daniel Otzen, Florian-Alexander Herbst, Per H Nielsen, Morten Dueholm, Hagan Bayley, Carol V Robinson, Stephen Hare, Stephen Matthews
Gram-negative bacteria possess specialised biogenesis machineries that facilitate the export of amyloid subunits for construction of a biofilm matrix. The secretion of bacterial functional amyloid requires a bespoke outer-membrane protein channel through which unfolded amyloid substrates are translocated. Here, we combine X-ray crystallography, native mass spectrometry, single-channel electrical recording, molecular simulations and circular dichroism measurements to provide high-resolution structural insight into the functional amyloid transporter from Pseudomonas, FapF...
August 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28733032/pilose-antler-peptide-potentiates-osteoblast-differentiation-and-inhibits-osteoclastogenesis-via-manipulating-the-nf-%C3%AE%C2%BAb-pathway
#2
Guangwang Liu, Chao Ma, Peian Wang, Peiying Zhang, Xinhua Qu, Shen Liu, Zanjing Zhai, Degang Yu, Juan Gao, Jun Liang, Weixiang Dai, Lindong Zhou, Mengjiao Xia, Huilin Yang
Bones are inflexible yet ever-changing metabolic organs, and bone homeostasis is maintained through two delicately regulated processes: bone construction and bone reabsorption. An imbalance in bone metabolism is linked to most orthopedic diseases, including osteoporosis and rheumatoid arthritis. Importantly, tumor necrosis factor-α (TNF-α) blocks osteoblast differentiation and stimulates osteoclast formation, resulting in delayed deposition of new bone and accelerated bone resorption, especially in rheumatoid arthritis patients with inflammatory conditions...
July 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28698048/identification-and-functional-evaluation-of-two-stat3-variants-in-grass-carp-implication-for-the-existence-of-specific-alternative-splicing-of-stat3-gene-in-teleost
#3
Linyong Du, Hong Zhou, Lei Qin, He Wei, Anying Zhang, Kun Yang, Xinyan Wang
A STAT family member, STAT3, becomes activated as a DNA binding protein in response to cytokines and growth factors. In teleost, STAT3 cDNA has been cloned and identified in a few species, but only a single STAT3 transcript is revealed in these studies. In the present study, two variants of STAT3 gene generated by alternative splicing were isolated from grass carp and nominated as STAT3α1 and STAT3α2 based on the homology with their mammalian orthologs. In particular, the homologs of STAT3α1/2 were also found in various fish species, including zebrafish, takifugu, tilapia, medaka and goldfish...
July 8, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28692601/recurrent-braf-gene-rearrangements-in-myxoinflammatory-fibroblastic-sarcomas-but-not-hemosiderotic-fibrolipomatous-tumors
#4
Yu-Chien Kao, Valentina Ranucci, Lei Zhang, Yun-Shao Sung, Edward A Athanasian, David Swanson, Brendan C Dickson, Cristina R Antonescu
Myxoinflammatory fibroblastic sarcoma (MIFS) is a low grade soft tissue sarcoma with a predilection for acral sites, being associated with a high rate of local recurrence but very infrequent distant metastases. Although a t(1;10) translocation resulting in TGFBR3-MGEA5 fusion has been reported as a recurrent genetic event in MIFS, this abnormality is seen only in a subset of cases. As no studies to date have investigated the spectrum of alternative genetic alterations in TGFBR3-MGEA5 fusion negative MIFS, we undertook a genetic analysis of this particular cohort for further molecular classification...
July 7, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28676202/hexacosanol-reduces-plasma-and-hepatic-cholesterol-by-activation-of-amp-activated-protein-kinase-and-suppression-of-sterol-regulatory-element-binding-protein-2-in-hepg2-and-c57bl-6j-mice
#5
Ji Hae Lee, Yaoyao Jia, Trung Thanh Thach, Yuri Han, Bobae Kim, Chunyan Wu, Yeonji Kim, Woo Duck Seo, Sung-Joon Lee
Policosanols have hypocholesterolemic activity; however, the molecular mechanism of the policosanol effects is currently poorly characterized. We hypothesized that hexacosanol, a policosanol compound derived from barley sprout, may decrease cellular and plasma cholesterol levels; we thus investigated the hypocholesterolemic activity and mechanism of hexacosanol on both hepatocytes and high-fat-induced obese C57BL/6J mice. The reduction of total cholesterol, free cholesterol, and cholesteryl ester concentrations was confirmed in hexacosanol-stimulated hepatocytes (-38%, -33%, and -53%, respectively)...
May 26, 2017: Nutrition Research
https://www.readbyqxmd.com/read/28660073/ryk-regulates-wnt5a-repulsion-of-mouse-corticospinal-tract-through-modulating-planar-cell-polarity-signaling
#6
Xin Duan, Yarong Gao, Yaobo Liu
It was previously reported a role for Ryk in mediating Wnt5a repulsion of the corticospinal tract (CST) in mice. Recent evidence has shown that Ryk regulates planar cell polarity (PCP) signaling through interacting with Vangl2. Here, in vivo, in vitro and biochemical analyses were applied to investigate the molecular cross-talk between the Ryk and PCP signaling pathways, revealing that PCP pathway components play important roles in CST anterior-posterior guidance. Ryk-Vangl2 interactions are crucial for PCP signaling to mediate Wnt5a repulsion of CST axons...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28659443/genetic-and-epigenetic-inactivation-of-sestrin1-controls-mtorc1-and-response-to-ezh2-inhibition-in-follicular-lymphoma
#7
Elisa Oricchio, Natalya Katanayeva, Maria Christine Donaldson, Stephanie Sungalee, Joyce P Pasion, Wendy Béguelin, Elena Battistello, Viraj R Sanghvi, Man Jiang, Yanwen Jiang, Matt Teater, Anita Parmigiani, Andrei V Budanov, Fong Chun Chan, Sohrab P Shah, Robert Kridel, Ari M Melnick, Giovanni Ciriello, Hans-Guido Wendel
Follicular lymphoma (FL) is an incurable form of B cell lymphoma. Genomic studies have cataloged common genetic lesions in FL such as translocation t(14;18), frequent losses of chromosome 6q, and mutations in epigenetic regulators such as EZH2 Using a focused genetic screen, we identified SESTRIN1 as a relevant target of the 6q deletion and demonstrate tumor suppression by SESTRIN1 in vivo. Moreover, SESTRIN1 is a direct target of the lymphoma-specific EZH2 gain-of-function mutation (EZH2(Y641X) ). SESTRIN1 inactivation disrupts p53-mediated control of mammalian target of rapamycin complex 1 (mTORC1) and enables mRNA translation under genotoxic stress...
June 28, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28628091/the-btg2-prmt1-module-limits-pre-b-cell-expansion-by-regulating-the-cdk4-cyclin-d3-complex
#8
Elmar Dolezal, Simona Infantino, Friedel Drepper, Theresa Börsig, Aparajita Singh, Thomas Wossning, Gina J Fiala, Susana Minguet, Bettina Warscheid, David M Tarlinton, Hassan Jumaa, David Medgyesi, Michael Reth
Developing pre-B cells in the bone marrow alternate between proliferation and differentiation phases. We found that protein arginine methyl transferase 1 (PRMT1) and B cell translocation gene 2 (BTG2) are critical components of the pre-B cell differentiation program. The BTG2-PRMT1 module induced a cell-cycle arrest of pre-B cells that was accompanied by re-expression of Rag1 and Rag2 and the onset of immunoglobulin light chain gene rearrangements. We found that PRMT1 methylated cyclin-dependent kinase 4 (CDK4), thereby preventing the formation of a CDK4-Cyclin-D3 complex and cell cycle progression...
August 2017: Nature Immunology
https://www.readbyqxmd.com/read/28608501/targeting-hypoxia-mediated-yap1-nuclear-translocation-ameliorates-pathogenesis-of-endometriosis-without-compromising-maternal-fertility
#9
Shih-Chieh Lin, Hsiu-Chi Lee, Pei-Chi Hou, Jhao-Lin Fu, Meng-Hsing Wu, Shaw-Jenq Tsai
Endometriosis is a highly prevalent gynecological disease that severely reduces women's health and quality of life. Ectopic endometriotic lesions have evolved mechanisms to survive in the hypoxic peritoneal microenvironment by regulating the expression of a significant subset of genes. However, the master regulator controlling these genes remains to be characterized. Herein, by using bioinformatics analysis and experimental verification, we identified Yes-Associated Protein 1 (YAP1) as a master regulator of endometriosis...
June 12, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28584094/reconstructing-blood-stem-cell-regulatory-network-models-from-single-cell-molecular-profiles
#10
Fiona K Hamey, Sonia Nestorowa, Sarah J Kinston, David G Kent, Nicola K Wilson, Berthold Göttgens
Adult blood contains a mixture of mature cell types, each with specialized functions. Single hematopoietic stem cells (HSCs) have been functionally shown to generate all mature cell types for the lifetime of the organism. Differentiation of HSCs toward alternative lineages must be balanced at the population level by the fate decisions made by individual cells. Transcription factors play a key role in regulating these decisions and operate within organized regulatory programs that can be modeled as transcriptional regulatory networks...
June 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28578400/lipid-droplet-associated-hydrolase-promotes-lipid-droplet-fusion-and-enhances-atgl-degradation-and-triglyceride-accumulation
#11
Young-Hwa Goo, Se-Hee Son, Antoni Paul
Lipid droplet (LD)-associated hydrolase (LDAH) is a newly identified LD protein abundantly expressed in tissues that predominantly store triacylglycerol (TAG). However, how LDAH regulates TAG metabolism remains unknown. We found that upon oleic acid loading LDAH translocalizes from the ER to newly formed LDs, and induces LD coalescence in a tubulin-dependent manner. LDAH overexpression and downregulation in HEK293 cells increase and decrease, respectively, TAG levels. Pulse and chase experiments show that LDAH enhances TAG biogenesis, but also decreases TAG turnover and fatty acid release from cells...
June 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28557017/novel-compounds-targeting-the-enterohemorrhagic-escherichia-coli-type-three-secretion-system-reveal-insights-into-mechanisms-of-secretion-inhibition
#12
Riccardo Zambelloni, James P R Connolly, Alejandro Huerta Uribe, Karl Burgess, Rodolfo Marquez, Andrew J Roe
Anti-virulence (AV) compounds are a promising alternative to traditional antibiotics for fighting bacterial infections. The Type Three Secretion System (T3SS) is a well-studied and attractive AV target, given that it is widespread in more than 25 species of Gram-negative bacteria, including enterohemorrhagic E. coli (EHEC), and as it is essential for host colonization by many pathogens. In this work, we designed, synthesized and tested a new series of compounds that block the functionality of the T3SS of EHEC...
May 29, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28556300/development-of-protein-degradation-inducers-of-oncogenic-bcr-abl-protein-by-conjugation-of-abl-kinase-inhibitors-and-iap-ligands
#13
Norihito Shibata, Naoki Miyamoto, Katsunori Nagai, Kenichiro Shimokawa, Tomoya Sameshima, Nobumichi Ohoka, Takayuki Hattori, Yasuhiro Imaeda, Hiroshi Nara, Nobuo Cho, Mikihiko Naito
Chromosomal translocation occurs in some cancer cells, which results in the expression of aberrant oncogenic fusion proteins that include BCR-ABL in chronic myelogenous leukemia (CML). Inhibitors of ABL tyrosine kinase, such as imatinib and dasatinib, exhibit remarkable therapeutic effects, although emergence of drug resistance hampers the therapy during long-term treatment. An alternative approach to treat CML is to downregulate the BCR-ABL protein. We have devised a protein knockdown system by hybrid molecules named Specific and Non-genetic inhibitor of apoptosis protein [IAP]-dependent Protein Erasers (SNIPER), which is designed to induce IAP-mediated ubiquitylation and proteasomal degradation of target proteins, and a couple of SNIPER(ABL) against BCR-ABL protein have been developed recently...
August 2017: Cancer Science
https://www.readbyqxmd.com/read/28543886/human-hairless-protein-roles-in-skin-hair-and-emerging-connections-to-brain-and-other-cancers
#14
Anas Maatough, G Kerr Whitfield, Lemlem Brook, David Hsieh, Patricia Palade, Jui-Cheng Hsieh
The mammalian hairless protein (HR) is a 130 kDa nuclear transcription factor that is essential for proper skin and hair follicle function. Previous studies have focused on the role of HR in skin maintenance and hair cycling. However, hairless gene (HR) is also expressed in brain and other tissues, where its role remains poorly understood. HR has been reported to contain functional domains that potentially serve in DNA binding, histone demethylation, nuclear translocation signal, and protein-protein interactions...
May 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28513634/mitochondria-targeted-platinum-ii-complexes-dual-inhibitory-activities-on-tumor-cell-proliferation-and-migration-invasion-via-intracellular-trafficking-of-%C3%AE-catenin
#15
Jingling Li, Xiaoli He, Yeling Zou, Dandan Chen, Liecheng Yang, Jiaming Rao, Huabing Chen, Michael C W Chan, Lin Li, Zhengqing Guo, Leshuai W Zhang, Chunying Chen
Mitochondria-targeted therapy is an alternative strategy for cancer therapy and may overcome the problems of metastasis and drug resistance that usually occur in conventional treatment. In this work, we demonstrate the mitochondria-targeted delivery of a cationic cyclometalated platinum(ii) complex, PIP-platin, in cancer cells. PIP-platin showed selective delivery and accumulation in the mitochondria and exhibited toxicity against a variety of tumor cell lines. The mitochondria were disrupted by PIP-platin, along with the generation of reactive oxygen species, depolarization of mitochondrial membrane potential, release of cytochrome c and necrosis...
June 21, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28512350/mechanisms-of-action-and-regulation-of-atp-dependent-chromatin-remodelling-complexes
#16
REVIEW
Cedric R Clapier, Janet Iwasa, Bradley R Cairns, Craig L Peterson
Cells utilize diverse ATP-dependent nucleosome-remodelling complexes to carry out histone sliding, ejection or the incorporation of histone variants, suggesting that different mechanisms of action are used by the various chromatin-remodelling complex subfamilies. However, all chromatin-remodelling complex subfamilies contain an ATPase-translocase 'motor' that translocates DNA from a common location within the nucleosome. In this Review, we discuss (and illustrate with animations) an alternative, unifying mechanism of chromatin remodelling, which is based on the regulation of DNA translocation...
July 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28503306/the-drive-to-generate-multiple-forms-of-oncogenic-cyclin-d1-transcripts-in-mantle-cell-lymphoma
#17
EDITORIAL
Chioniso Patience Masamha
Alternative polyadenylation is a rapidly emerging form of gene regulation, which in its simplest form, enables the generation of mRNA transcripts that code for the same protein but have 3'UTRs of different lengths and regulatory content. For oncogenes, shorter 3'UTRs would be preferred as a mechanism to evade miRNA regulation. The shortening of the 3'UTR of cyclin D1 in mantle cell lymphoma offers provocative insights into this process. Patient samples have revealed that 3'UTR shortening may occur due to mutations, or translocations that result in the generation of a chimeric 3'UTR...
2017: Biomarker Research
https://www.readbyqxmd.com/read/28467182/roles-of-silent-information-regulator-1-serine-arginine-rich-splicing-factor-10-lipin-1-axis-in-the-pathogenesis-of-alcohol-fatty-liver-disease
#18
REVIEW
Yuanyuan Li, Junying Zhou
Alcohol exposure is a major reason of morbidity and mortality all over the world, with much of detrimental consequences attributing to alcoholic liver disease (ALD). With the continued ethanol consumption, alcoholic fatty liver disease (AFLD, the earliest and reversible form of ALD) can further develop to more serious forms of alcoholic liver damage, including alcoholic steatohepatitis, fibrosis/cirrhosis, and even eventually progress to hepatocellular carcinoma and liver failure. Furthermore, cell trauma, inflammation, oxidative stress, regeneration, and bacterial translocation are crucial promoters of ethanol-mediated liver lesions...
June 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28465491/discovery-and-characterization-of-small-molecules-targeting-the-dna-binding-ets-domain-of-erg-in-prostate-cancer
#19
Miriam S Butler, Mani Roshan-Moniri, Michael Hsing, Desmond Lau, Ari Kim, Paul Yen, Marta Mroczek, Mannan Nouri, Scott Lien, Peter Axerio-Cilies, Kush Dalal, Clement Yau, Fariba Ghaidi, Yubin Guo, Takeshi Yamazaki, Sam Lawn, Martin E Gleave, Cheryl Y Gregory-Evans, Lawrence P McIntosh, Michael E Cox, Paul S Rennie, Artem Cherkasov
Genomic alterations involving translocations of the ETS-related gene ERG occur in approximately half of prostate cancer cases. These alterations result in aberrant, androgen-regulated production of ERG protein variants that directly contribute to disease development and progression. This study describes the discovery and characterization of a new class of small molecule ERG antagonists identified through rational in silico methods. These antagonists are designed to sterically block DNA binding by the ETS domain of ERG and thereby disrupt transcriptional activity...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28447783/real-time-detection-reveals-responsive-cotranscriptional-formation-of-persistent-intramolecular-dna-and-intermolecular-dna-rna-hybrid-g-quadruplexes-stabilized-by-r-loop
#20
Yang Zhao, Jia-Yu Zhang, Zong-Yu Zhang, Tan-Jun Tong, Yu-Hua Hao, Zheng Tan
G-quadruplex (GQ) structures are implicated in important physiological and pathological processes. Millions of GQ-forming motifs are enriched near transcription start sites (TSSs) of animal genes. Transcription can induce the formation of GQs, which in turn regulate transcription. The kinetics of the formation and persistence of GQs in transcription is crucial for the role they play but has not yet been explored. We established a method based on the fluorescence resonance energy transfer (FRET) technique to monitor in real-time the cotranscriptional formation and post-transcriptional persistence of GQs in DNA...
June 6, 2017: Analytical Chemistry
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