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Regulated Alternative Translocation

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https://www.readbyqxmd.com/read/29304433/probing-the-interaction-mechanisms-between-transmembrane-peptides-and-the-chaperonin-groel-with-fluorescence-anisotropy
#1
Xiaoqiang Wang, Han Chen, Xinwei Lu, Haixia Chi, Shixin Li, Fang Huang
Proper translocation, membrane insertion and folding are crucial biophysical steps in the biogenesis of functional transmembrane peptides/proteins (TMPs). ATP-dependent chaperonins are able to regulate each of these processes, but the underlying mechanisms remain unclear. In this work, interaction between the bacterial chaperonin GroEL and a synthetic fluorescent transmembrane peptide was investigated by fluorescence anisotropy. Binding of the peptide with GroEL resulted in increased fluorescence anisotropy and intensity...
December 29, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/29246902/identification-of-the-coagulation-factor-viia-integrin-binding-site-required-for-pro-angiogenic-par2-signaling
#2
Andrea S Rothmeier, Enbo Liu, Sagarika Chakrabarty, Jennifer Disse, Barbara M Mueller, Henrik Østergaard, Wolfram Ruf
The tissue factor (TF) pathway serves both hemostasis and cell signaling, but how cells control these divergent functions of TF remains incompletely understood. TF is the receptor and scaffold of coagulation proteases cleaving protease activated receptor (PAR) 2 that plays pivotal roles in angiogenesis and tumor development. Here we demonstrate that coagulation factor (F) VIIa elicits TF cytoplasmic domain-dependent pro-angiogenic cell signaling independent of the alternative PAR2 activator matriptase. We identify a Lys-Gly-Glu (KGE) integrin binding motif in the FVIIa protease domain that is required for association of the TF-FVIIa complex with the active conformer of integrin β1...
December 15, 2017: Blood
https://www.readbyqxmd.com/read/29246543/oncostatin-m-upregulates-hif-1%C3%AE-in-breast-tumor-associated-macrophages-independent-of-intracellular-oxygen-concentration
#3
Richa Shrivastava, Varsha Singh, Mohammad Asif, Mahendra Pal Singh Negi, Smrati Bhadauria
AIMS: HIF is an important transcription-regulator for adaptation to cellular stress in cells of myeloid origin. Classically, expression and activity of HIF1-α is regulated by oxygen-concentration within cell. However, there exists an alternative regulatory mechanism affecting HIF1-α levels independent of oxygen concentration particularly in inflammatory cells like macrophages. Here we report the mechanism of HIF1-α upregulation in TAMs by Oncostatin-M (OSM) independent of cellular oxygen concentration...
December 12, 2017: Life Sciences
https://www.readbyqxmd.com/read/29241544/dissociation-of-rad51-presynaptic-complexes-and-heteroduplex-dna-joints-by-tandem-assemblies-of-srs2
#4
Kyle Kaniecki, Luisina De Tullio, Bryan Gibb, Youngho Kwon, Patrick Sung, Eric C Greene
Srs2 is a superfamily 1 (SF1) helicase and antirecombinase that is required for genome integrity. However, the mechanisms that regulate Srs2 remain poorly understood. Here, we visualize Srs2 as it acts upon single-stranded DNA (ssDNA) bound by the Rad51 recombinase. We demonstrate that Srs2 is a processive translocase capable of stripping thousands of Rad51 molecules from ssDNA at a rate of ∼50 monomers/s. We show that Srs2 is recruited to RPA clusters embedded between Rad51 filaments and that multimeric arrays of Srs2 assemble during translocation on ssDNA through a mechanism involving iterative Srs2 loading events at sites cleared of Rad51...
December 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/29237756/the-prokaryotic-na-ca2-exchanger-ncx_mj-transports-na-and-ca2-in-a-3-1-stoichiometry
#5
Irina Shlosman, Fabrizio Marinelli, José D Faraldo-Gómez, Joseph A Mindell
Intracellular Ca2+ signals control a wide array of cellular processes. These signals require spatial and temporal regulation of the intracellular Ca2+ concentration, which is achieved in part by a class of ubiquitous membrane proteins known as sodium-calcium exchangers (NCXs). NCXs are secondary-active antiporters that power the translocation of Ca2+ across the cell membrane by coupling it to the flux of Na+ in the opposite direction, down an electrochemical gradient. Na+ and Ca2+ are translocated in separate steps of the antiport cycle, each of which is thought to entail a mechanism whereby ion-binding sites within the protein become alternately exposed to either side of the membrane...
December 13, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/29229835/o-glcnacylation-destabilizes-the-active-tetrameric-pkm2-to-promote-the-warburg-effect
#6
Yang Wang, Jia Liu, Xin Jin, Dapeng Zhang, Dongxue Li, Fengqi Hao, Yunpeng Feng, Shan Gu, Fanlin Meng, Miaomiao Tian, Yi Zheng, Ling Xin, Xinbo Zhang, Xue Han, L Aravind, Min Wei
The Warburg effect, characterized by increased glucose uptake and lactate production, is a well-known universal across cancer cells and other proliferating cells. PKM2, a splice isoform of the pyruvate kinase (PK) specifically expressed in these cells, serves as a major regulator of this metabolic reprogramming with an adjustable activity subjected to numerous allosteric effectors and posttranslational modifications. Here, we have identified a posttranslational modification on PKM2, O-GlcNAcylation, which specifically targets Thr405 and Ser406, residues of the region encoded by the alternatively spliced exon 10 in cancer cells...
December 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29227555/combining-fluorescence-and-bioluminescence-microscopy-to-study-the-series-of-events-from-cellular-signal-transduction-to-gene-expression
#7
Kazuhito Goda, Takeo Takahashi, Hirobumi Suzuki
The molecular interactions and translocation of signal transduction factors in individual cells can be imaged by fluorescence microscopy. Alternatively, downstream promoter activity in single cells can be imaged by bioluminescence microscopy. However, the same stimuli can lead to different gene expression responses in individual cells. For this reason, it is desirable to simultaneously image signal transduction and gene expression events in the same cells. Here, we describe a method that combines fluorescence and bioluminescence microscopy to image protein kinase C (PKC) translocation from the cytosol to the plasma membrane and the expression of nuclear factor kappa-light polypeptide B (NF-κB)-regulated genes...
December 11, 2017: Current Protocols in Cell Biology
https://www.readbyqxmd.com/read/29187515/nrf2-at-the-heart-of-oxidative-stress-and-cardiac-protection
#8
Qin M Chen, Anthony J Maltagliati
The NFE2L2 gene encodes the transcription factor Nrf2 best known for regulating the expression of antioxidant and detoxification genes. Gene knockout approaches have demonstrated its universal cytoprotective features. While Nrf2 has been the topic of intensive research in cancer biology since its discovery in 1994, understanding the role of Nrf2 in cardiovascular disease has just begun. The literature concerning Nrf2 in experimental models of atherosclerosis, ischemia, reperfusion, cardiac hypertrophy, heart failure, and diabetes supports its cardiac protective character...
November 29, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/29162741/nuclear-hyaluronidase-2-drives-alternative-splicing-of-cd44-pre-mrna-to-determine-profibrotic-or-antifibrotic-cell-phenotype
#9
Adam C Midgley, Sebastian Oltean, Vincent Hascall, Emma L Woods, Robert Steadman, Aled O Phillips, Soma Meran
The cell surface protein CD44 is involved in diverse physiological processes, and its aberrant function is linked to various pathologies such as cancer, immune dysregulation, and fibrosis. The diversity of CD44 biological activity is partly conferred by the generation of distinct CD44 isoforms through alternative splicing. We identified an unexpected function for the ubiquitous hyaluronan-degrading enzyme, hyaluronidase 2 (HYAL2), as a regulator of CD44 splicing. Standard CD44 is associated with fibrotic disease, and its production is promoted through serine-arginine-rich (SR) protein-mediated exon exclusion...
November 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/29158982/genome-wide-in-silico-identification-of-membrane-bound-transcription-factors-in-plant-species
#10
Shixiang Yao, Lili Deng, Kaifang Zeng
Membrane-bound transcription factors (MTFs) are located in cellular membranes due to their transmembrane domains. In plants, proteolytic processing is considered to be the main mechanism for MTF activation, which ensures the liberation of MTFs from membranes and further their translocation into the nucleus to regulate gene expression; this process skips both the transcriptional and translational stages, and thus it guarantees the prompt responses of plants to various stimuli. Currently, information concerning plant MTFs is limited to model organisms, including Arabidopsis thaliana and Oryza sativa, and little is known in other plant species at the genome level...
2017: PeerJ
https://www.readbyqxmd.com/read/29156304/water-management-regimes-alter-pb-uptake-and-translocation-in-fragrant-rice
#11
Umair Ashraf, Saddam Hussain, Nadeem Akbar, Shakeel Ahmad Anjum, Waseem Hassan, Xiangru Tang
Rice cultivation in lead (Pb) polluted soils often leads to high Pb contents in rice grains. The present study investigated the dynamics of Pb uptake under different water regimes in two fragrant rice cultivars i.e., Guixiangzhan and Nongxiang-18. Results revealed that water dynamics regulated the antioxidant activities in both rice cultivars under Pb toxicity. Compared to continuous ponding (CP), taken as control, alternate wetting and drying (AWD) reduced the Pb contents in roots, stems, leaves, and grains up to 17%, 41%, 22%, and 52% in Guixiangzhan and 23%, 19%, 17%, and 37% in Nongxiang-18, respectively...
November 17, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/29155216/communication-between-genomic-and-non-genomic-signaling-events-coordinate-steroid-hormone-actions
#12
Sandi R Wilkenfeld, Chenchu Lin, Daniel E Frigo
Steroid hormones are lipophilic molecules produced in one cell that can travel great distances within the body to elicit biological effects in another cell. In the canonical pathway, steroid hormone binding to a nuclear receptor (NR), often in the cytoplasm, causes the receptor to undergo a conformational change and translocate to the nucleus, where it interacts with specific sequences of DNA to regulate transcription. In addition to the classical genomic mechanism of action, alternate mechanisms of steroid activity have emerged that involve rapid, non-genomic signaling...
November 16, 2017: Steroids
https://www.readbyqxmd.com/read/29091322/a-novel-diterpenoid-suppresses-osteoclastogenesis-and-promotes-osteogenesis-by-inhibiting-ifrd1-and-i%C3%AE%C2%BAb%C3%AE-mediated-p65-nuclear-translocation
#13
Zi'ang Xie, Hejun Yu, Xuewu Sun, Pan Tang, Zhiwei Jie, Shuai Chen, Jiying Wang, An Qin, Shunwu Fan
Osteoporosis develops due to impaired bone formation and/or excessive bone resorption. Although the pharmacological treatment of osteoporosis has been extensively developed, alternative treatments are still needed. Here, we showed that oridonin (ORI), a diterpenoid isolated from Rabdosia rubescens, can suppress osteoclastogenesis and enhance osteogenesis. ORI inhibited the receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclast formation and bone resorption through the inhibition of p65 nuclear translocation...
November 1, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29077485/the-splicing-factor-hnrnpa1-regulates-alternate-splicing-of-the-mylk-gene
#14
Joseph B Mascarenhas, Alex Y Tchourbanov, Sergei M Danilov, Tong Zhou, Ting Wang, Joe G N Garcia
Profound lung vascular permeability is a cardinal feature of Acute Respiratory Distress Syndrome (ARDS) and Ventilator-Induced Lung injury (VILI), two syndromes known to centrally involve the non-muscle isoform of myosin light chain kinase (nmMLCK) in vascular barrier dysregulation. Two main splice variants, nmMLCK1 and nmMLCK2, are well represented in human lung endothelial cells and encoded by MYLK and differ only in the presence of exon 11 in nmMLCK1 which contains critical phosphorylation sites (Y464 and Y471) that influence nmMLCK enzymatic activity, cellular translocation, and localization in response to vascular agonists...
October 27, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29058711/the-helicase-domain-of-pol%C3%AE-counteracts-rpa-to-promote-alt-nhej
#15
Pedro A Mateos-Gomez, Tatiana Kent, Sarah K Deng, Shane McDevitt, Ekaterina Kashkina, Trung M Hoang, Richard T Pomerantz, Agnel Sfeir
Mammalian polymerase theta (Polθ) is a multifunctional enzyme that promotes error-prone DNA repair by alternative nonhomologous end joining (alt-NHEJ). Here we present structure-function analyses that reveal that, in addition to the polymerase domain, Polθ-helicase activity plays a central role during double-strand break (DSB) repair. Our results show that the helicase domain promotes chromosomal translocations by alt-NHEJ in mouse embryonic stem cells and also suppresses CRISPR-Cas9- mediated gene targeting by homologous recombination (HR)...
October 23, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/29033244/iaspp-is-an-antioxidative-factor-and-drives-cancer-growth-and-drug-resistance-by-competing-with-nrf2-for-keap1-binding
#16
Wenjie Ge, Kunming Zhao, Xingwen Wang, Huayi Li, Miao Yu, Mengmeng He, Xuting Xue, Yifu Zhu, Cheng Zhang, Yiwei Cheng, Shijian Jiang, Ying Hu
Reactive oxygen species (ROS) have emerged as important signaling molecules that play crucial roles in carcinogenesis and cytotoxic responses. Nrf2 is the master regulator of ROS balance. Thus, uncovering mechanisms of Nrf2 regulation is important for the development of alternative treatment strategies for cancers. Here, we demonstrate that iASPP, a known p53 inhibitor, lowers ROS independently of p53. Mechanistically, iASPP competes with Nrf2 for Keap1 binding via a DLT motif, leading to decreased Nrf2 ubiquitination and increased Nrf2 accumulation, nuclear translocation, and antioxidative transactivation...
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29031599/interaction-of-dj-1-with-lyn-is-essential-for-ige-mediated-stimulation-of-human-mast-cells
#17
Do-Kyun Kim, Michael A Beaven, Dean D Metcalfe, Ana Olivera
BACKGROUND: DJ-1 is a redox-sensitive protein with multiple roles in cell homeostasis whose levels are altered in mast cell (MC)-related disorders. However, whether DJ-1 can regulate human MC function is unknown. OBJECTIVE: We sought to investigate the potential role of DJ-1 in the responses of human MCs to antigen stimulation. METHODS: DJ-1 was silenced in human CD34(+)-derived and LAD2 MCs using lentiviral sh-RNA constructs. Release of β-hexosaminidase, PGD2 and GM-CSF and changes in reactive oxygen species (ROS) levels were measured after FcεRI engagement...
October 12, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29027792/multifunctional-cytochrome-c-learning-new-tricks-from-an-old-dog
#18
REVIEW
Damián Alvarez-Paggi, Luciana Hannibal, María A Castro, Santiago Oviedo-Rouco, Veronica Demicheli, Veronica Tórtora, Florencia Tomasina, Rafael Radi, Daniel H Murgida
Cytochrome c (cyt c) is a small soluble heme protein characterized by a relatively flexible structure, particularly in the ferric form, such that it is able to sample a broad conformational space. Depending on the specific conditions, interactions, and cellular localization, different conformations may be stabilized, which differ in structure, redox properties, binding affinities, and enzymatic activity. The primary function is electron shuttling in oxidative phosphorylation, and is exerted by the so-called native cyt c in the intermembrane mitochondrial space of healthy cells...
November 8, 2017: Chemical Reviews
https://www.readbyqxmd.com/read/29021383/wnt-%C3%AE-catenin-promoted-macrophage-alternative-activation-contributes-to-kidney-fibrosis
#19
Ye Feng, Jiafa Ren, Yuan Gui, Wei Wei, Bingyan Shu, Qingmiao Lu, Xian Xue, Xiaoli Sun, Weichun He, Junwei Yang, Chunsun Dai
The Wnt/β-catenin pathway is crucial in normal development and throughout life, but aberrant activation of this pathway has been linked to kidney fibrosis, although the mechanisms involved remain incompletely determined. Here, we investigated the role of Wnt/β-catenin in regulating macrophage activation and the contribution thereof to kidney fibrosis. Treatment of macrophages with Wnt3a exacerbated IL-4- or TGFβ1-induced macrophage alternative (M2) polarization and the phosphorylation and nuclear translocation of STAT3 in vitro Conversely, inhibition of Wnt/β-catenin signaling prevented these IL-4- or TGFβ1-induced processes...
October 11, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28986802/re-expressing-epigenetically-silenced-genes-by-inducing-dna-demethylation-through-targeting-of-ten-eleven-translocation-2-to-any-given-genomic-locus
#20
Julio Cesar Rendón, David Cano-Rodríguez, Marianne G Rots
Epigenetic editing is a novel methodology to modify the epigenetic landscape of any genomic location. As such, the approach might reprogram expression profiles, without altering the DNA sequence. Epigenetic alterations, including promoter hypermethylation, are associated with an increasing number of human diseases. To exploit this situation, epigenetic editing rises as a new alternative to specifically demethylate abnormally hypermethylated regions. Here, we describe a methodology to actively demethylate the hypermethylated ICAM-1 promoter...
2017: Methods in Molecular Biology
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