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Regulated Alternative Translocation

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https://www.readbyqxmd.com/read/27933067/peptide-idr-1002-inhibits-nf-%C3%AE%C2%BAb-nuclear-translocation-by-inhibition-of-i%C3%AE%C2%BAb%C3%AE-degradation-and-activates-p38-erk1-2-msk1-dependent-creb-phosphorylation-in-macrophages-stimulated-with-lipopolysaccharide
#1
Alejandro Huante-Mendoza, Octavio Silva-García, Javier Oviedo-Boyso, Robert E W Hancock, Víctor M Baizabal-Aguirre
The inflammatory response is a critical molecular defense mechanism of the innate immune system that mediates the elimination of disease-causing bacteria. Repair of the damaged tissue, and the reestablishment of homeostasis, must be accomplished after elimination of the pathogen. The innate defense regulators (IDRs) are short cationic peptides that mimic natural host defense peptides and are effective in eliminating pathogens by enhancing the activity of the immune system while controlling the inflammatory response...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27888447/the-regulation-of-the-mitochondrial-apoptotic-pathway-by-glucocorticoid-receptor-in-collaboration-with-bcl-2-family-proteins-in-developing-t-cells
#2
Lilla Prenek, Ferenc Boldizsár, Réka Kugyelka, Emese Ugor, Gergely Berta, Péter Németh, Timea Berki
Glucocorticoids (GC) are important in the regulation of selection and apoptosis of CD4(+)CD8(+) double-positive (DP) thymocytes. The pronounced GC-sensitivity of DP thymocytes, observed earlier, might be due to the combination of classical (genomic) and alternative (non-genomic) glucocorticoid receptor (GR) signaling events modifying activation or apoptotic pathways. In particular, the previously demonstrated mitochondrial translocation of activated GR in DP thymocytes offered a fascinating explanation for their pronounced GC-induced apoptosis sensitivity...
November 26, 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27814612/mirnas-as-drivers-of-tmprss2-erg-negative-prostate-tumors-in-african-american-men
#3
Clayton Yates, Mark D Long, Moray J Campbell, Lara Sucheston-Campbell
African Americans (AAs) who have PCa typically have more aggressive disease and make up a disproportionate number of the disease deaths, relative to European Americans (EAs). TMPRSS2 translocations, a common event in EA patients, are exploited in diagnostic and prognostic settings, whereas they are diminished in frequency in AA men. Thus, these patients with TMPRSS2 fusion-negative disease represent an under-investigated patient group. We propose that epigenetic events are a significant and alternative driver of aggressive disease in fusion-negative PCa...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27813153/traf6-mediates-suppression-of-osteoclastogenesis-and-prevention-of-ovariectomy-induced-bone-loss-by-a-novel-prenylflavonoid
#4
E M Tan, L Li, I R Indran, N Chew, E L Yong
Given the limitations of current therapeutic options for postmenopausal osteoporosis, there is a need for alternatives with minimal adverse effects. In this study, we evaluated the effects of icaritin (ICT), a natural prenylflavonoid, on osteoclastogenesis both in vitro and in an ovariectomized (OVX)-rat model, and investigated its underlying molecular mechanism(s) of action. ICT inhibited osteoclast formation in two osteoclast precursor models, RAW 264.7 mouse monocyte cell line and human PBMC. ICT also inhibited sealing zone and resorption pit formation in a dose-dependent manner...
November 4, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/27807651/comparison-of-the-alendronate-and-irradiation-with-a-light-emitting-diode-led-on-murine-osteoclastogenesis
#5
Hong Moon Sohn, Youngjong Ko, Mineon Park, Bora Kim, Jung Eun Park, Donghwi Kim, Young Lae Moon, Wonbong Lim
Photomodulation therapy (PBMT) using light-emitting diode (LED) has been proposed as an alternative to conventional osteoporosis therapies. Our aim was to determine the effect of irradiation with a light-emitting diode on receptor activator of NF-κB ligand (RANKL)-mediated differentiation of mouse bone marrow macrophages into osteoclasts and compare it to alendronate treatment. The cells were irradiated with LED at 635±10 nm, 9-cm spot size, 5 mW/cm(2), and 18 J for 60 min/day in a CO2 incubator. The differentiation of irradiated and untreated RANKL-stimulated bone marrow macrophages into osteoclasts was evaluated by tartrate-resistant acid phosphatase (TRAP) staining and by molecular methods...
November 2, 2016: Lasers in Medical Science
https://www.readbyqxmd.com/read/27799473/ef-g-catalyzed-translocation-dynamics-in-the-presence-of-ribosomal-frameshifting-stimulatory-signals
#6
Hee-Kyung Kim, Ignacio Tinoco
Programmed -1 ribosomal frameshifting (-1PRF) is tightly regulated by messenger RNA (mRNA) sequences and structures in expressing two or more proteins with precise ratios from a single mRNA. Using single-molecule fluorescence resonance energy transfer (smFRET) between (Cy5)EF-G and (Cy3)tRNA(Lys), we studied the translational elongation dynamics of -1PRF in the Escherichia coli dnaX gene, which contains three frameshifting signals: a slippery sequence (A AAA AAG), a Shine-Dalgarno (SD) sequence and a downstream hairpin...
October 30, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27794497/ucp1-a-sophisticated-energy-valve
#7
REVIEW
Martin Klingenberg
This review focuses on the biochemical work of UCP1 starting from the early observation by Ricquier and Kader in 1976. We entered this field in 1980 with the isolation of native UCP1 and then reported the amino acid sequence structure discovering a strong homology to the ADP/ATP carrier. With the isolated native UCP1 we studied structural and functional features, in particular the complex characteristics of nucleotide binding. A strong pH dependence of binding and herein the differences between diphopho- and triphopho-nucleotides were observed, resulting in the identification of residues which control binding site access by their H(+) dissociation...
October 26, 2016: Biochimie
https://www.readbyqxmd.com/read/27791164/structural-basis-for-dynamic-regulation-of-the-human-26s-proteasome
#8
Shuobing Chen, Jiayi Wu, Ying Lu, Yong-Bei Ma, Byung-Hoon Lee, Zhou Yu, Qi Ouyang, Daniel J Finley, Marc W Kirschner, Youdong Mao
The proteasome is the major engine of protein degradation in all eukaryotic cells. At the heart of this machine is a heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitylated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides. Using cryoelectron microscopy, we determined a near-atomic-resolution structure of the 2.5-MDa human proteasome in its ground state, as well as subnanometer-resolution structures of the holoenzyme in three alternative conformational states...
November 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27764820/on-01910-na-rigosertib-inhibits-pi3k-akt-pathway-and-activates-oxidative-stress-signals-in-head-and-neck-cancer-cell-lines
#9
Anil Prasad, Nagina Khudaynazar, Ramana V Tantravahi, Amanda M Gillum, Benjamin S Hoffman
Squamous cell carcinoma of the head and neck (HNSCC) is characterized by high morbidity and mortality. Treatment failure, drug resistance and chemoradiation toxicity have necessitated the development of alternative treatment strategies. Styryl benzyl sulfones, a family of novel small molecule inhibitors, are being evaluated as anti-neoplastic agents in multiple clinical trials. The activity of these compounds has been well characterized in several preclinical tumor studies, but their activity has yet to be fully examined in HNSCC...
October 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27730540/downregulation-of-smurf2-ubiquitin-ligase-in-pancreatic-cancer-cells-reversed-tgf-%C3%AE-induced-tumor-formation
#10
Bo Wu, Bomin Guo, Jie Kang, Xianzhao Deng, Youben Fan, Xiaoping Zhang, Kaixing Ai
Smad ubiquitin regulatory factor 2 (Smurf2) is an E3 ubiquitin ligase that regulates transforming growth factor β (TGF-β)/Smad signaling and is implicated in a wide range of cellular responses. However, the exact mechanism whereby Smurf2 controls TGF-β-induced signaling pathways remains unknown. Here, we identified the relationship between the alternate TGF-β signaling pathways: TGF-β/PI3K/Akt/β-catenin and TGF-β/Smad2/3/FoxO1/PUMA and Smurf2. The results showed that TGF-β promoted proliferation, invasion, and migration of human pancreatic carcinoma (PANC-1) cells through the PI3K/Akt/β-catenin pathway...
October 11, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27727273/zfp423-regulates-sonic-hedgehog-signaling-via-primary-cilium-function
#11
Chen-Jei Hong, Bruce A Hamilton
Zfp423 encodes a 30-zinc finger transcription factor that intersects several canonical signaling pathways. Zfp423 mutations result in ciliopathy-related phenotypes, including agenesis of the cerebellar vermis in mice and Joubert syndrome (JBTS19) and nephronophthisis (NPHP14) in humans. Unlike most ciliopathy genes, Zfp423 encodes a nuclear protein and its developmental expression is complex, leading to alternative proposals for cellular mechanisms. Here we show that Zfp423 is expressed by cerebellar granule cell precursors, that loss of Zfp423 in these precursors leads to cell-intrinsic reduction in proliferation, loss of response to Shh, and primary cilia abnormalities that include diminished frequency of both Smoothened and IFT88 localization...
October 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27709780/construction-of-asymmetrical-hexameric-biomimetic-motors-with-continuous-single-directional-motion-by-sequential-coordination
#12
Zhengyi Zhao, Hui Zhang, Dan Shu, Carlo Montemagno, Baoquan Ding, Jingyuan Li, Peixuan Guo
The significance of bionanomotors in nanotechnology is analogous to mechanical motors in daily life. Here the principle and approach for designing and constructing biomimetic nanomotors with continuous single-directional motion are reported. This bionanomotor is composed of a dodecameric protein channel, a six-pRNA ring, and an ATPase hexamer. Based on recent elucidations of the one-way revolving mechanisms of the phi29 double-stranded DNA (dsDNA) motor, various RNA and protein elements are designed and tested by single-molecule imaging and biochemical assays, with which the motor with active components has been constructed...
October 6, 2016: Small
https://www.readbyqxmd.com/read/27694897/systematic-and-functional-characterization-of-novel-androgen-receptor-variants-arising-from-alternative-splicing-in-the-ligand-binding-domain
#13
T Uo, H Dvinge, C C Sprenger, R K Bradley, P S Nelson, S R Plymate
The presence of intact ligand-binding domain (LBD) ensures the strict androgen-dependent regulation of androgen receptor (AR): binding of androgen induces structural reorganization of LBD resulting in release of AR from HSP90, suppression of nuclear export which otherwise dominates over import and nuclear translocation of AR as a transcription factor. Thus, loss or defects of the LBD abolish constraint from un-liganded LBD as exemplified by constitutively active AR variants (AR-Vs), which are associated with emerging resistance mechanism to anti-AR therapy in castration-resistant prostate cancer (mCRPC)...
October 3, 2016: Oncogene
https://www.readbyqxmd.com/read/27669037/substrate-translocating-loops-regulate-mechanochemical-coupling-and-power-production-in-aaa-protease-clpxp
#14
Piere Rodriguez-Aliaga, Luis Ramirez, Frank Kim, Carlos Bustamante, Andreas Martin
ATP-dependent proteases of the AAA+ family, including Escherichia coli ClpXP and the eukaryotic proteasome, contribute to maintenance of cellular proteostasis. ClpXP unfolds and translocates substrates into an internal degradation chamber, using cycles of alternating dwell and burst phases. The ClpX motor performs chemical transformations during the dwell and translocates the substrate in increments of 1-4 nm during the burst, but the processes occurring during these phases remain unknown. Here we characterized the complete mechanochemical cycle of ClpXP, showing that ADP release and ATP binding occur nonsequentially during the dwell, whereas ATP hydrolysis and phosphate release occur during the burst...
November 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27575692/contribution-of-cyclic-and-pseudo-cyclic-electron-transport-to-the-formation-of-proton-motive-force-in-chloroplasts
#15
REVIEW
Toshiharu Shikanai, Hiroshi Yamamoto
Photosynthetic electron transport is coupled to proton translocation across the thylakoid membrane, resulting in the formation of a trans-thylakoid proton gradient (ΔpH) and membrane potential (Δψ). Ion transporters and channels localized to the thylakoid membrane regulate the contribution of each component to the proton motive force (pmf). Although both ΔpH and Δψ contribute to ATP synthesis as pmf, only ΔpH downregulates photosynthetic electron transport via the acidification of the thylakoid lumen by inducing thermal dissipation of excessive absorbed light energy from photosystem II antennae and slowing down of the electron transport through the cytochrome b6f complex...
August 26, 2016: Molecular Plant
https://www.readbyqxmd.com/read/27574533/spatial-distribution-of-lipid-droplets-during-starvation-implications-for-lipophagy
#16
Antonio Daniel Barbosa, Symeon Siniossoglou
Survival during starvation depends largely on metabolic energy, which is stored in the form of neutral lipids in specialized organelles known as lipid droplets. The precursors for the synthesis of neutral lipids are also used for membrane biogenesis, which is required for cell growth and proliferation. Therefore cells must possess mechanisms to preferentially channel lipid precursors toward either membrane synthesis or lipid droplet storage, in response to nutrient status. How this partitioning is spatially regulated within the endoplasmic reticulum (ER) where lipid droplets co-localize, remains poorly understood...
July 2016: Communicative & Integrative Biology
https://www.readbyqxmd.com/read/27548565/h3k36-methyltransferases-as-cancer-drug-targets-rationale-and-perspectives-for-inhibitor-development
#17
David S Rogawski, Jolanta Grembecka, Tomasz Cierpicki
Methylation at histone 3, lysine 36 (H3K36) is a conserved epigenetic mark regulating gene transcription, alternative splicing and DNA repair. Genes encoding H3K36 methyltransferases (KMTases) are commonly overexpressed, mutated or involved in chromosomal translocations in cancer. Molecular biology studies have demonstrated that H3K36 KMTases regulate oncogenic transcriptional programs. Structural studies of the catalytic SET domain of H3K36 KMTases have revealed intriguing opportunities for design of small molecule inhibitors...
September 2016: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/27499293/inverting-the-topology-of-a-transmembrane-protein-by-regulating-the-translocation-of-the-first-transmembrane-helix
#18
Qiuyue Chen, Bray Denard, Ching-En Lee, Sungwon Han, James S Ye, Jin Ye
TM4SF20 (transmembrane 4 L6 family 20) is a polytopic membrane protein that inhibits proteolytic processing of CREB3L1 (cAMP response element-binding protein 3-like 1), a membrane-bound transcription factor that blocks cell division and activates collagen synthesis. Here we report that ceramide stimulates CREB3L1 cleavage by inverting the orientation of TM4SF20 in membranes. In the absence of ceramide, the N terminus of the first transmembrane helix of TM4SF20 is inserted into the endoplasmic reticulum (ER) lumen...
August 18, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27457952/supraphysiologic-levels-of-the-aml1-eto-isoform-ae9a-are-essential-for-transformation
#19
Kevin A Link, Shan Lin, Mahesh Shrestha, Melissa Bowman, Mark Wunderlich, Clara D Bloomfield, Gang Huang, James C Mulloy
Chromosomal translocation 8;21 is found in 40% of the FAB M2 subtype of acute myeloid leukemia (AML). The resultant in-frame fusion protein AML1-ETO (AE) acts as an initiating oncogene for leukemia development. AE immortalizes human CD34(+) cord blood cells in long-term culture. We assessed the transforming properties of the alternatively spliced AE isoform AE9a (or alternative splicing at exon 9), which is fully transforming in a murine retroviral model, in human cord blood cells. Full activity was realized only upon increased fusion protein expression...
August 9, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27412581/inhibition-of-the-injectisome-and-flagellar-type-iii-secretion-systems-by-inp1855-impairs-pseudomonas-aeruginosa-pathogenicity-and-inflammasome-activation
#20
Ahalieyah Anantharajah, Emmanuel Faure, Julien M Buyck, Charlotta Sundin, Tuulikki Lindmark, Joan Mecsas, Timothy L Yahr, Paul M Tulkens, Marie-Paule Mingeot-Leclercq, Benoît Guery, Françoise Van Bambeke
With the rise of multidrug resistance, Pseudomonas aeruginosa infections require alternative therapeutics. The injectisome (iT3SS) and flagellar (fT3SS) type III secretion systems are 2 virulence factors associated with poor clinical outcomes. iT3SS translocates toxins, rod, needle, or regulator proteins, and flagellin into the host cell cytoplasm and causes cytotoxicity and NLRC4-dependent inflammasome activation, which induces interleukin 1β (IL-1β) release and reduces interleukin 17 (IL-17) production and bacterial clearance...
October 1, 2016: Journal of Infectious Diseases
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