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https://www.readbyqxmd.com/read/28231469/bassoon-controls-presynaptic-autophagy-through-atg5
#1
Nathan D Okerlund, Katharina Schneider, Sergio Leal-Ortiz, Carolina Montenegro-Venegas, Sally A Kim, Loren C Garner, Eckart D Gundelfinger, Richard J Reimer, Craig C Garner
Mechanisms regulating the surveillance and clearance of synaptic proteins are not well understood. Intriguingly, the loss of the presynaptic active zone proteins Piccolo and Bassoon triggers the loss of synaptic vesicles (SVs) and compromises synaptic integrity. Here we report that the destruction of SVs in boutons lacking Piccolo and Bassoon was associated with the induction of presynaptic autophagy, a process that depended on poly-ubiquitination, but not the E3 ubiquitin ligase Siah1. Surprisingly, gain or loss of function (LOF) of Bassoon alone suppressed or enhanced presynaptic autophagy, respectively, implying a fundamental role for Bassoon in the local regulation of presynaptic autophagy...
February 22, 2017: Neuron
https://www.readbyqxmd.com/read/28231341/identification-of-the-er-resident-e3-ubiquitin-ligase-rnf145-as-a-novel-lxr-regulated-gene
#2
Emma C L Cook, Jessica K Nelson, Vincenzo Sorrentino, Duco Koenis, Martina Moeton, Saskia Scheij, Roelof Ottenhoff, Boris Bleijlevens, Anke Loregger, Noam Zelcer
Cellular cholesterol metabolism is subject to tight regulation to maintain adequate levels of this central lipid molecule. Herein, the sterol-responsive Liver X Receptors (LXRs) play an important role owing to their ability to reduce cellular cholesterol load. In this context, identifying the full set of LXR-regulated genes will contribute to our understanding of their role in cholesterol metabolism. Using global transcriptional analysis we report here the identification of RNF145 as an LXR-regulated target gene...
2017: PloS One
https://www.readbyqxmd.com/read/28230160/global-view-of-cognate-kinase-activation-by-the-human-pyruvate-dehydrogenase-complex
#3
Elena L Guevara, Luying Yang, Barbara Birkaya, Jieyu Zhou, Natalia S Nemeria, Mulchand S Patel, Frank Jordan
The human pyruvate dehydrogenase complex (PDC) comprises four multidomain components, E1, E3, E2 and an E3-binding protein (E3BP), the latter two forming the core as E2·E3BP sub-complex. Pyruvate flux through PDC is regulated via phosphorylation (inactivation) at E1 by four PDC kinases (PDKs), and reactivation by two PDC phosphatases. Up-regulation of PDK isoform gene expression is reported in several forms of cancer, while PDKs may be further activated by PDC by binding to the E2·E3BP core. Hence, the PDK: E2·E3BP interaction provides new therapeutic targets...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28230156/drebrin-mediated-microtubule-actomyosin-coupling-steers-cerebellar-granule-neuron-nucleokinesis-and-migration-pathway-selection
#4
Niraj Trivedi, Daniel R Stabley, Blake Cain, Danielle Howell, Christophe Laumonnerie, Joseph S Ramahi, Jamshid Temirov, Ryan A Kerekes, Phillip R Gordon-Weeks, David J Solecki
Neuronal migration from a germinal zone to a final laminar position is essential for the morphogenesis of neuronal circuits. While it is hypothesized that microtubule-actomyosin crosstalk is required for a neuron's 'two-stroke' nucleokinesis cycle, the molecular mechanisms controlling such crosstalk are not defined. By using the drebrin microtubule-actin crosslinking protein as an entry point into the cerebellar granule neuron system in combination with super-resolution microscopy, we investigate how these cytoskeletal systems interface during migration...
February 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28229491/osnla1-a-ring-type-ubiquitin-ligase-maintains-phosphate-homeostasis-in-oryza-sativa-via-degradation-of-phosphate-transporters
#5
Wenhao Yue, Yinghui Ying, Chuang Wang, Yang Zhao, Changhe Dong, James Whelan, Huixia Shou
Inorganic phosphate (Pi) transporters (PTs) play vital roles in Pi uptake and translocation in plants. Under Pi sufficient conditions, PTs are degraded to prevent excess Pi accumulation. The mechanisms targeting PTs for degradation are not fully elucidated. In this study, we found that the Oryza sativa (rice) ortholog of Arabidopsis thaliana Nitrogen Limitation Adaptation (NLA), OsNLA1 protein, a RING-type E3 ubiquitin-ligase, was predominantly localized in the plasma membrane, and could interact with rice phosphate transporters OsPT2 and OsPT8...
February 23, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28228265/e3-ligase-rnf126-directly-ubiquitinates-frataxin-promoting-its-degradation-identification-of-a-potential-therapeutic-target-for-friedreich-ataxia
#6
Monica Benini, Silvia Fortuni, Ivano Condò, Giulia Alfedi, Florence Malisan, Nicola Toschi, Dario Serio, Damiano Sergio Massaro, Gaetano Arcuri, Roberto Testi, Alessandra Rufini
Friedreich ataxia (FRDA) is a severe genetic neurodegenerative disease caused by reduced expression of the mitochondrial protein frataxin. To date, there is no therapy to treat this condition. The amount of residual frataxin critically affects the severity of the disease; thus, attempts to restore physiological frataxin levels are considered therapeutically relevant. Frataxin levels are controlled by the ubiquitin-proteasome system; therefore, inhibition of the frataxin E3 ligase may represent a strategy to achieve an increase in frataxin levels...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28228263/reciprocal-regulation-between-53bp1-and-the-anaphase-promoting-complex-cyclosome-is-required-for-genomic-stability-during-mitotic-stress
#7
Thomas J Kucharski, Paul E Minshall, Mohamed Moustafa-Kamal, Andrew S Turnell, Jose G Teodoro
The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that targets substrates for degradation to promote mitotic progression. Here, we show that the DNA damage response protein 53BP1 contains conserved KEN boxes that are required for APC/C-dependent degradation in early mitosis. Mutation of the 53BP1 KEN boxes stabilized the protein and extended mitotic duration, whereas 53BP1 knockdown resulted in a shorter and delayed mitosis. Loss of 53BP1 increased APC/C activity, and we show that 53BP1 is a direct APC/C inhibitor...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28225217/proteomic-analysis-of-the-cullin4b-interactome-using-proximity-dependent-biotinylation-in-living-cells
#8
Hailong Zhang, Shupeng Li, Pingting Liu, Frankie H F Lee, Albert H C Wong, Fang Liu
Cullin 4B (CUL4B) mutations have been implicated in mental retardation and dopamine-related behaviors due to disruptions in their interaction with Cullin-RING E3 ligases (CRLs). Thus, further identification of CUL4B substrates can increase the knowledge of protein homeostasis and illuminate the role of CUL4B in neuropsychiatric disease. However, the transient nature of the coupling between CUL4B and its substrates is difficult to detect in vivo using current approaches, thus hampers efforts to investigate functions of CRLs within unperturbed living systems...
February 22, 2017: Proteomics
https://www.readbyqxmd.com/read/28224243/simultaneous-quantitation-of-endogenous-estrone-17%C3%AE-estradiol-and-estriol-in-human-serum-by-isotope-dilution-liquid-chromatography-tandem-mass-spectrometry-for-clinical-laboratory-applications
#9
Qiaoxuan Zhang, Liqiao Han, Jianbing Wang, Haibiao Lin, Peifeng Ke, Junhua Zhuang, Xianzhang Huang
Estrogen measurements are important in the assessment of female reproductive function and have expanding roles in other fields. A simple, accurate, highly sensitive and specific isotope-dilution liquid chromatography-tandem mass spectrometry method was developed and evaluated to simultaneously measure three endogenous estrogens in serum: estrone (E1), 17β-estradiol (E2), and estriol (E3). Chromatographic separation was achieved on a C18 column before electrospray ionization triple-quadrupole mass spectrometry in multiple reaction monitoring mode...
February 21, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28224045/dj-1-maintains-energy-and-glucose-homeostasis-by-regulating-the-function-of-brown-adipose-tissue
#10
Rong Wu, Xiao-Meng Liu, Jian-Guang Sun, Hong Chen, Jun Ma, Meng Dong, Shengyi Peng, Ji-Qiu Wang, Jian-Qing Ding, Dong-Hao Li, John R Speakman, Guang Ning, Wanzhu Jin, Zengqiang Yuan
DJ-1 protein is involved in multiple physiological processes, including Parkinson's disease. However, the role of DJ-1 in the metabolism is largely unknown. Here we found that DJ-1 maintained energy balance and glucose homeostasisvia regulating brown adipose tissue (BAT) activity. DJ-1-deficient mice reduced body mass, increased energy expenditure and improved insulin sensitivity. DJ-1 deletion also resisted high-fat-diet (HFD) induced obesity and insulin resistance. Accordingly, DJ-1 transgene triggered autonomous obesity and glucose intolerance...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28223714/comparative-physiological-and-transcriptomic-analyses-provide-integrated-insight-into-osmotic-cold-and-salt-stress-tolerance-mechanisms-in-banana
#11
Wei Hu, Zehong Ding, Weiwei Tie, Yan Yan, Yang Liu, Chunlai Wu, Juhua Liu, Jiashui Wang, Ming Peng, Biyu Xu, Zhiqiang Jin
The growth, development, and production of banana plants are constrained by multiple abiotic stressors. However, it remains elusive for the tolerance mechanisms of banana responding to multiple abiotic stresses. In this study, we found that Fen Jiao (FJ) was more tolerant to osmotic, cold, and salt stresses than BaXi Jiao (BX) by phenotypic and physiological analyses. Comparative transcriptomic analyses highlighted stress tolerance genes that either specifically regulated in FJ or changed more than twofold in FJ relative to BX after treatments...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28223312/natural-variation-and-dosage-of-the-hei10-meiotic-e3-ligase-control-arabidopsis-crossover-recombination
#12
Piotr A Ziolkowski, Charles J Underwood, Christophe Lambing, Marina Martinez-Garcia, Emma J Lawrence, Liliana Ziolkowska, Catherine Griffin, Kyuha Choi, F Chris H Franklin, Robert A Martienssen, Ian R Henderson
During meiosis, homologous chromosomes undergo crossover recombination, which creates genetic diversity and balances homolog segregation. Despite these critical functions, crossover frequency varies extensively within and between species. Although natural crossover recombination modifier loci have been detected in plants, causal genes have remained elusive. Using natural Arabidopsis thaliana accessions, we identified two major recombination quantitative trait loci (rQTLs) that explain 56.9% of crossover variation in Col×Ler F2 populations...
February 21, 2017: Genes & Development
https://www.readbyqxmd.com/read/28223226/targeted-protein-degradation-by-protacs
#13
REVIEW
Taavi K Neklesa, James D Winkler, Craig M Crews
Targeted protein degradation using the PROTAC technology is emerging as a novel therapeutic method to address diseases driven by the aberrant expression of a disease-causing protein. PROTAC molecules are bifunctional small molecules that simultaneously bind a target protein and an E3-ubiquitin ligase, thus causing ubiquitination and degradation of the target protein by the proteasome. Like small molecules, PROTAC molecules possess good tissue distribution and the ability to target intracellular proteins. Herein, we highlight the advantages of protein degradation using PROTACs, and provide specific examples where degradation offers therapeutic benefit over classical enzyme inhibition...
February 13, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28222786/post-translational-modification-of-parkin
#14
REVIEW
Joy Chakraborty, Valentina Basso, Elena Ziviani
: Mutations in the gene encoding for the E3 ubiquitin ligase Parkin are associated to a rare form of familiar autosomal recessive Parkinsonism. Despite decades of research on the Parkin protein, whose structure has been recently solved, little is known about the specific signalling pathways that lead to Parkin activation. Parkin activity spans from mitochondria quality control to tumor suppression and stress protection; it is thus tempting to hypothesize that the broad impact of Parkin on cellular physiology might be the result of different post translational modifications that can be controlled by balanced opposing events...
February 21, 2017: Biology Direct
https://www.readbyqxmd.com/read/28220688/the-dnaj-protein-osdja6-negatively-regulates-rice-innate-immunity-to-the-blast-fungus-magnaporthe-oryzae
#15
Xionghui Zhong, Jiuxia Yang, Yanlong Shi, Xuli Wang, Guo-Liang Wang
Rice blast, caused by Magnaporthe oryzae (synonym: Pyricularia oryzae), severely reduces rice production and grain quality. The molecular mechanism of rice resistance to M. oryzae is not fully understood. In the present study, we identified a chaperone DnaJ protein, OsDjA6, that is involved in basal resistance to M. oryzae in rice. The OsDjA6 protein is distributed in the entire rice cell. The expression of OsDjA6 is significantly induced in rice after infection with a compatible isolate. Silencing of OsDjA6 in transgenic rice enhances resistance to M...
February 21, 2017: Molecular Plant Pathology
https://www.readbyqxmd.com/read/28220068/reduced-activity-in-the-right-inferior-frontal-gyrus-in-elderly-apoe-e4-carriers-during-a-verbal-fluency-task
#16
Andrea Katzorke, Julia B M Zeller, Laura D Müller, Martin Lauer, Thomas Polak, Andreas Reif, Jürgen Deckert, Martin J Herrmann
Apolipoprotein-E4 (APOE-E4) is a major genetic risk factor for developing Alzheimer's disease (AD). The verbal fluency task (VFT), especially the subtask category fluency, has shown to provide a good discrimination between cognitively normal controls and subjects with AD. Interestingly, APOE-E4 seems to have no effect on the behavioral performance during a VFT in healthy elderly. Thus, the purpose of the present study was to reveal possible compensation mechanisms by investigating the effect of APOE-E4 on the hemodynamic response in non-demented elderly during a VFT by using functional near-infrared spectroscopy (fNIRS)...
2017: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/28218735/aurora-kinase-a-regulates-survivin-stability-through-targeting-fbxl7-in-gastric-cancer-drug-resistance-and-prognosis
#17
M Kamran, Z-J Long, D Xu, S-S Lv, B Liu, C-L Wang, J Xu, E W-F Lam, Q Liu
Aurora kinase A (AURKA) has been implicated in the regulation of cell cycle progression, mitosis and a key number of oncogenic signaling pathways in various malignancies. However, little is known about its role in gastric cancer prognosis and genotoxic resistance. Here we found that AURKA was highly overexpressed in gastric cancer and inversely correlated with disease prognosis. Overexpression of AURKA exacerbated gastric cancer drug resistance through upregulating the expression of the anti-apoptotic protein Survivin...
February 20, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28218667/essential-roles-of-e3-ubiquitin-ligases-in-p53-regulation
#18
REVIEW
Sanam Sane, Khosrow Rezvani
The ubiquitination pathway and proteasomal degradation machinery dominantly regulate p53 tumor suppressor protein stability, localization, and functions in both normal and cancerous cells. Selective E3 ubiquitin ligases dominantly regulate protein levels and activities of p53 in a large range of physiological conditions and in response to cellular changes induced by exogenous and endogenous stresses. The regulation of p53's functions by E3 ubiquitin ligases is a complex process that can lead to positive or negative regulation of p53 protein in a context- and cell type-dependent manner...
February 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28216678/the-cul3-spop-daxx-axis-is-a-novel-regulator-of-vegfr2-expression-in-vascular-endothelial-cells
#19
Tomohisa Sakaue, Iori Sakakibara, Takahiro Uesugi, Ayako Fujisaki, Koh-Ichi Nakashiro, Hiroyuki Hamakawa, Eiji Kubota, Takashi Joh, Yu-Ki Imai, Hironori Izutani, Shigeki Higashiyama
Vascular endothelial cell growth factor receptor 2 (VEGFR2) is an essential receptor for the homeostasis of endothelial cells. In this study, we showed that NEDD8-conjugated Cullin3 (CUL3)-based ubiquitin E3 (UbE3) ligase plays a crucial role in VEGFR2 mRNA expression. Human umbilical vein endothelial cells treated with MLN4924, an inhibitor of NEDD8-activating enzyme, or with CUL3 siRNA drastically lost their response to VEGF due to the intense decrease in VEGFR2 expression. Moreover, speckle-type POZ protein (SPOP) and death-domain associated protein (DAXX) were involved in the CUL3 UbE3 ligase complex as a substrate adaptor and a substrate, respectively...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28216640/the-ubiquitin-ligase-cullin5-socs2-regulates-ndr1-stk38-stability-and-nf-%C3%AE%C2%BAb-transactivation
#20
Indranil Paul, Tanveer S Batth, Diego Iglesias-Gato, Amna Al-Araimi, Ibrahim Al-Haddabi, Amira Alkharusi, Gunnar Norstedt, Jesper V Olsen, Fahad Zadjali, Amilcar Flores-Morales
SOCS2 is a pleiotropic E3 ligase. Its deficiency is associated with gigantism and organismal lethality upon inflammatory challenge. However, mechanistic understanding of SOCS2 function is dismal due to our unawareness of its protein substrates. We performed a mass spectrometry based proteomic profiling upon SOCS2 depletion and yield quantitative data for ~4200 proteins. Through this screen we identify a novel target of SOCS2, the serine-threonine kinase NDR1. Over-expression of SOCS2 accelerates turnover, while its knockdown stabilizes, endogenous NDR1 protein...
February 20, 2017: Scientific Reports
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