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Journal of Biological Chemistry

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https://www.readbyqxmd.com/read/28821623/proteolytic-cleavage-by-the-imp-complex-or-oct1-peptidase-controls-the-localization-of-the-yeast-peroxiredoxin-prx1-to-distinct-mitochondrial-compartments
#1
Fernando Gomes, Flavio Romero Palma, Mario H Barros, Eduardo T Tsuchida, Helena G Turano, Thiago G P Alegria, Marilene Demasi, Luis E S Netto
Yeast Prx1 is a mitochondrial 1-Cys peroxiredoxin that catalyzes the reduction of endogenously generated H2O2 Prx1 is synthesized on cytosolic ribosomes as a preprotein with a cleavable N-terminal presequence that is the mitochondrial targeting signal, but the mechanisms underlying Prx1 distribution to distinct mitochondrial subcompartments are unknown. Here, we provide direct evidence of the following dual mitochondrial localization of Prx1: a soluble form in the intermembrane space and a form in the matrix weakly associated with the inner mitochondrial membrane...
August 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28821621/protein-kinase-g-confers-survival-advantage-to-mycobacterium-tuberculosis-during-latency-like-conditions
#2
Mehak Zahoor Khan, Ashima Bhaskar, Sandeep Upadhyay, Pooja Kumari, Raju S Rajmani, Preeti Jain, Amit Singh, Dhiraj Kumar, Neel Sarovar Bhavesh, Vinay Kumar Nandicoori
Protein Kinase G (PknG), a thioredoxin-fold containing eukaryotic like serine/threonine protein kinase (STPK), is a virulence factor in the Mycobacterium tuberculosis, required for inhibition of phago-lysosomal fusion. Here, we unravelled novel functional facets of PknG during latency like conditions. We find that PknG mediates persistence under stressful conditions like hypoxia and abets drug tolerance. PknG mutant displayed minimal growth in nutrient limiting conditions suggesting its role in modulating cellular metabolism...
August 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28821620/arjunolic-acid-a-peroxisome-proliferator-activated-receptor-alpha-agonist-regresses-cardiac-fibrosis-by-inhibiting-non-canonical-tgf-%C3%AE-signaling
#3
Trisha Bansal, Emeli Chatterjee, Jasdeep Singh, Arjun Ray, Bishwajit Kundu, V Thankamani, Shantanu Sengupta, Sagartirtha Sarkar
Cardiac hypertrophy and associated heart fibrosis remain a major cause of death worldwide. Phytochemicals have gained attention as alternative therapeutics for managing cardiovascular diseases. These include the extract from the plant Terminalia arjuna which is a popular cardioprotectant and may prevent or slow progression of pathological hypertrophy to heart failure. Here, we investigated the mode of action of a principal bioactive T. arjuna compound, arjunolic acid (AA) in ameliorating hemodynamic load-induced cardiac fibrosis and identified its intracellular target...
August 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28821619/dsc-e3-ligase-localization-to-the-golgi-requires-the-atpase-cdc48-and-cofactor-ufd1-for-activation-of-sterol-regulatory-element-binding-protein-in-fission-yeast
#4
Risa Burr, Diedre Ribbens, Sumana Raychaudhuri, Emerson V Stewart, Jason Ho, Peter J Espenshade
Sterol regulatory element-binding proteins (SREBPs) in the fission yeast Schizosaccharomyces pombe regulate lipid homeostasis and the hypoxic response under conditions of low sterol or oxygen availability. SREBPs are cleaved in the Golgi through the combined action of the Dsc E3 ligase complex, the rhomboid protease Rbd2, and the essential ATPases Associated with diverse cellular Activities (AAA+) ATPase Cdc48. The soluble SREBP N-terminal transcription factor domain is then released in the cytosol to enter the nucleus and regulate gene expression...
August 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28821609/insulin-like-growth-factor-1-signalling-is-essential-for-mitochondrial-biogenesis-and-mitophagy-in-cancer-cells
#5
Amy Lyons, Michael Coleman, Sarah Riis, Cedric Favre, Ciara H O'Flanagan, Alexander V Zhdanov, Dmitri B Papkovsky, Stephen D Hursting, Rosemary O'Connor
Mitochondrial activity and metabolic reprogramming influence the phenotype of cancer cells and resistance to targeted therapy. We previously established that an Insulin-like Growth Factor 1 (IGF-1)-inducible mitochondrial UTP carrier (PNC1/SLC25A33) promotes cell growth. This prompted us to investigate whether IGF signaling is essential for mitochondrial maintenance in cancer cells, and whether this contributes to therapy resistance. Here, we show that IGF-1 stimulates mitochondrial biogenesis in a range of cell lines...
August 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28821607/two-plant-derived-aporphinoid-alkaloids-exert-their-antifungal-activity-by-disrupting-mitochondrial-iron-sulfur-cluster-biosynthesis
#6
Siddharth K Tripathi, Tao Xu, Qin Feng, Bharathi Avula, Xiaomin Shi, Xuewen Pan, Melanie M Mask, Scott R Baerson, Melissa R Jacob, Ranga Rao Ravu, Shabana I Khan, Xing-Cong Li, Ikhlas A Khan, Alice M Clark, Ameeta K Agarwal
Eupolauridine and liriodenine are plant-derived aporphinoid alkaloids that exhibit potent inhibitory activity against the opportunistic fungal pathogens Candida albicans and Cryptococcus neoformans However, the molecular mechanism of this antifungal activity is unknown. In this study, we show that eupolauridine 9591 (E9591), a synthetic analog of eupolauridine, and liriodenine methiodide (LMT), a methiodide salt of liriodenine, mediate their antifungal activities by disrupting mitochondrial iron-sulfur (Fe-S) cluster synthesis...
August 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28821617/janus-kinase-3-regulates-adherens-junction-and-epithelial-mesenchymal-transition-through-beta-catenin
#7
Jayshree Mishra, Jugal Kishore Das, Narendra Kumar
Compromise in adherens junction (AJ) is associated with several chronic inflammatory diseases. Previously we reported that Janus kinase-3, a non-receptor tyrosine kinase plays a crucial role in AJ formation through its interaction with beta-catenin. In this report, we characterize the structural determinants responsible for Jak3 interactions with beta-catenin and determine the functional implications of previously unknown tyrosine residues on beta-catenin phosphorylated by Jak3. We demonstrate that Jak3 auto-phosphorylation was the rate- limiting step during Jak3 trans-phosphorylation of beta-catenin where Jak3 directly phosphorylated three tyrosine residues viz...
August 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28821608/the-transmembrane-domain-of-the-p75-neurotrophin-receptor-stimulates-phosphorylation-of-the-trkb-tyrosine-kinase-receptor
#8
Khalil Saadipour, Michael MacLean, Sean Pirkle, Solav Ali, Maria Luisa Lopez-Redondo, David L Stokes, Moses V Chao
The function of protein products generated from intramembraneous cleavage by the γ-secretase complex is not well defined. The γ-secretase complex is responsible for the cleavage of several transmembrane proteins, most notably the amyloid precursor protein which results in Aβ, a transmembrane (TM) peptide. Another protein that undergoes a very similar γ-secretase cleavage is the p75 neurotrophin receptor. However, the fate of the cleaved p75 TM domain is unknown. p75 neurotrophin receptor is highly expressed during early neuronal development and regulates survival and process formation of neurons...
August 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28821616/cox16-protein-is-physically-associated-with-cox1p-assembly-intermediates-and-with-cytochrome-oxidase
#9
Chen Hsien Su, Alexander Tzagoloff
Mitochondrial cytochrome oxidase (COX) catalyzes the last step in the respiratory pathway. In Saccharomyces cervisiae this inner membrane complex is composed of 11 protein subunits. Expression of COX is assisted by some 2 dozen ancillary proteins that intercede at different stages of the assembly pathway. One such protein, Cox16p, encoded by COX16, was shown to be essential for activity and assembly of COX. The function of Cox16p, however, has not been determined. We present evidence that Cox16p is present in Cox1p assembly intermediates and in COX...
August 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28821613/the-rir-motif-in-the-scaffold-protein-xrcc1-mediates-a-low-affinity-interaction-with-polynucleotide-kinase-phosphatase-pnkp-during-dna-single-strand-break-repair
#10
Claire Breslin, Rajam S Mani, Mesfin Fanta, Nicolas Hoch, Michael Weinfeld, Keith W Caldecott
The scaffold protein X-ray repair cross-complementing 1 (XRCC1) interacts with multiple enzymes involved in DNA base excision repair and single-strand break repair (SSBR) and is important for genetic integrity and normal neurological function. One of the most important interactions of XRCC1 is that with polynucleotide kinase/phosphatase (PNKP), a dual-function DNA kinase/phosphatase that processes damaged DNA termini and that, if mutated, results in ataxia with oculomotor apraxia 4 (AOA4) and microcephaly with early-onset seizures and developmental delay (MCSZ)...
August 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28821612/syndecan-2-cytoplasmic-domain-upregulates-matrix-metalloproteinase-7-expression-via-protein-kinasec%C3%AE-mediated-fak-erk-signaling-pathway-in-colon-cancer
#11
Bohee Jang, Hyejung Jung, Sojoong Choi, Young Hun Lee, Seung-Taek Lee, Eok-Soo Oh
The syndecan family of heparan sulfate proteoglycans contribute to cell adhesion and communication by serving as co-receptors for cell signaling and extracellular matrix molecules. Syndecan-2 is located at the cell surface, and we previously reported that it induces matrix metalloproteinase-7 (MMP-7) expression in colon cancer cells. However, the underlying regulatory mechanisms are unknown. Here, we report that over-expression of syndecan-2 in HT-29 colon cancer cells increases the phosphorylation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK) in parallel with upregulated MMP-7 expression, but a syndecan-2 mutant lacking the cytoplasmic domain showed significant reductions in these effects...
August 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28821610/a-screen-for-kinase-inhibitors-identifies-antimicrobial-imidazopyridine-aminofurazans-as-specific-inhibitors-of-the-listeria-monocytogenes-pasta-kinase-prka
#12
Adam J Schaenzer, Nathan Wlodarchak, David H Drewry, William J Zuercher, Warren E Rose, Rob Striker, John-Demian Sauer
Bacterial signaling systems such as protein kinases and quorum sensing have become increasingly attractive targets for the development of novel antimicrobial agents in a time of rising antibiotic resistance. The family of bacterial Penicillin-binding-protein And Serine/Threonine kinase-Associated (PASTA) kinases is of particular interest due to the role of these kinases in regulating resistance to β-lactam antibiotics. As such, small-molecule kinase inhibitors that target PASTA kinases may prove beneficial as treatments adjunctive to β-lactam therapy...
August 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28821622/the-replication-and-transcription-activator-of-murine-gammaherpesvirus-68-cooperatively-enhances-cytokine-activated-stat3-mediated-gene-expression
#13
Hui-Chen Chang Foreman, Julie Armstrong, Alexis L Santana, Laurie T Krug, Nancy C Reich
Gammaherpesviruses (γΗVs) have a dynamic strategy for life-time persistence, involving productive infection, latency, and intermittent reactivation. In latency reservoirs, such as B lymphocytes, γΗV exists as a viral episome and expresses few viral genes. Although the ability of γHV to reactivate from latency and re-enter the lytic phase is challenging to investigate and control, it is known that the γΗV replication and transcription activator, RTA, can promote lytic reactivation. In this study, we provide first evidence that RTA of murine γΗV 68 (MHV68) selectively binds and enhances the activity of tyrosine-phosphorylated host STAT3...
August 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28821618/region-specific-protein-misfolding-cyclic-amplification-reproduces-brain-tropism-of-prion-strains
#14
Nicolas Privat, Etienne Levavasseur, Serfildan Yildirim, Samia Hannaoui, Jean-Philippe Brandel, Jean-Louis Laplanche, Vincent Béringue, Danielle Seilhean, Stéphane Haïk
Human prion diseases such as Creutzfeldt-Jakob disease are transmissible brain proteinopathies, characterized by the accumulation of a misfolded isoform of the host cellular prion protein (PrP) in the brain. According to the prion model, prions are defined as proteinaceous infectious particles composed solely of this abnormal isoform of PrP (PrPSc). Even in the absence of genetic material, various prion strains can be propagated in experimental models. They can be distinguished by the pattern of disease they produce and especially by the localization of PrPSc deposits within the brain and the spongiform lesions they induce...
August 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28821615/distinct-structural-mechanisms-determine-substrate-affinity-and-kinase-activity-of-protein-kinase-c%C3%AE
#15
Sangbae Lee, Titu Devamani, Hyun Deok Song, Manbir Sandhu, Adrien Larsen, Ruth Sommese, Abhinandan Jain, Nagarajan Vaidehi, Sivaraj Sivaramakrishnan
Protein kinase Cα (PKCα) belongs to the family of AGC kinases that phosphorylate multiple peptide substrates. While the consensus sequence motif has been identified and used to explain substrate specificity for PKCα, it does not inform the structural basis of substrate binding and kinase activity for diverse substrates phosphorylated by this kinase. The transient, dynamic, and unstructured nature of this protein-protein interaction has limited structural mapping of kinase-substrate interfaces. Here, using multiscale MD simulation-based predictions and FRET sensor-based experiments, we investigated the conformational dynamics of the kinase-substrate interface...
August 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28821614/multiple-circadian-transcriptional-elements-cooperatively-regulate-cell-autonomous-transcriptional-oscillation-of-period3-a-mammalian-clock-gene
#16
Ritsuko Matsumura, Makoto Akashi
Cell-autonomous oscillation in clock gene expression drives circadian rhythms. The development of comprehensive analytical techniques, such as bioinformatics and ChIP-sequencing, has enabled the genome-wide identification of potential circadian transcriptional elements that regulate the transcriptional oscillation of clock genes. However, detailed analyses using traditional biochemical and molecular-biological approaches, such as binding and reporter assays, are still necessary to determine whether these potential circadian transcriptional elements are actually functional and how significantly they contribute to driving transcriptional oscillation...
August 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28821611/the-proteasome-interacting-ecm29-protein-disassembles-the-26s-proteasome-in-response-to-oxidative-stress
#17
Xiaorong Wang, Ilan E Chemmama, Clinton Yu, Alexander Huszagh, Yue Xu, Rosa Viner, Sarah Ashley Block, Peter Cimermancic, Scott D Rychnovsky, Yihong Ye, Andrej Sali, Lan Huang
Oxidative stress has been implicated in multiple human neurological and other disorders. Proteasomes are multi-subunit proteases critical for the removal of oxidatively damaged proteins. To understand stress-associated human pathologies, it is important to uncover the molecular events underlying the regulation of proteasomes upon oxidative stress. To this end, we investigated H2O2 stress-induced molecular changes of the human 26S proteasome and determined that stress-induced 26S proteasome disassembly is conserved from yeast to human...
August 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28808064/obesity-and-aging-diminish-sirt1-mediated-deacetylation-of-sirt3-leading-to-hyperacetylation-and-decreased-activity-and-stability-of-sirt3
#18
Sanghoon Kwon, Sunmi Seok, Peter Yau, Xiaoling Li, Byron Kemper, Jongsook Kim Kemper
Sirtuin 3 (SIRT3) deacetylates and regulates many mitochondrial proteins to maintain health, but its functions are depressed in aging and obesity. The best-studied sirtuin, SIRT1, counteracts aging- and obesity-related diseases by deacetylating many proteins, but whether SIRT1 has a role in deacetylating and altering the function of SIRT3 is unknown. Here we show that SIRT3 is reversibly acetylated in the mitochondria and unexpectedly is a target of SIRT1 deacetylation. SIRT3 is hyperacetylated in aged and obese mice, in which SIRT1 activity is low, and SIRT3 acetylation at K57 inhibits its deacetylase activity and promotes protein degradation...
August 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28808063/phylogenetic-sequence-analysis-and-functional-studies-reveal-compensatory-amino-acid-substitutions-in-loop-2-of-human-ribonucleotide-reductase
#19
Andrew J Knappenberger, Sneha Grandhi, Reena Sheth, Md Faiz Ahmad, Rajesh Viswanathan, Michael E Harris
Eukaryotic class I ribonucleotide reductases (RRs) generate deoxyribonucleotides for DNA synthesis. Binding of dNTP effectors is coupled to the formation of active dimers and induces conformational changes in a short loop (loop 2) to regulate RR's specificity among its nucleoside diphosphate (NDP) substrates. Moreover, ATP and dATP bind at an additional allosteric site 40 Å away from loop 2 and thereby drive formation of activated or inactive hexamers, respectively. To better understand how dNTP binding influences specificity, activity, and oligomerization of human RR, we aligned >300 eukaryotic RR sequences to examine natural sequence variation in loop 2...
August 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28808062/ablating-tbc1d1-impairs-contraction-induced-sarcolemmal-glucose-transporter-type-4-redistribution-but-not-insulin-mediated-responses-in-rats
#20
Jamie Whitfield, Sabina Paglialunga, Brennan K Smith, Paula M Miotto, Genevieve Simnett, Holly L Robson, Swati S Jain, Eric A F Herbst, Eric M Desjardins, David J Dyck, Lawrence L Spriet, Gregory R Steinberg, Graham P Holloway
TBC1 domain family member 1 (TBC1D1), a Rab GTPase-activating protein and paralogue of Akt substrate of 160 kDa (AS160), has been implicated in both insulin- and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (AICAR)-mediated glucose transporter type (GLUT4) translocation. However, the role of TBC1D1 in contracting muscle remains ambiguous. We therefore explored the metabolic consequence of ablating TBC1D1 in both resting and contracting skeletal muscles, utilizing a rat TBC1D1-KO model...
August 14, 2017: Journal of Biological Chemistry
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