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https://www.readbyqxmd.com/read/29168928/regulation-of-kv1-4-potassium-channels-by-pkc-and-ampk-kinases
#1
Martin Nybo Andersen, Lasse Skibsbye, Arnela Saljic, Martin Zahle Larsen, Hanne Borger Rasmussen, Thomas Jespersen
Over the last years extensive kinase-mediated regulation of a number of voltage-gated potassium (Kv) channels important in cardiac electrophysiology has been reported. This includes regulation of Kv1.5, Kv7.1 and Kv11.1 cell surface expression, where the kinase-mediated regulation appears to center around the ubiquitin ligase Nedd4-2. In the present study we examined whether Kv1.4, constituting the cardiac Ito,s current, is subject to similar regulation. In the epithelial Madin-Darby Canine Kidney (MDCK) cell line, which constitutes a highly reproducible model system for addressing membrane targeting, we find, by confocal microscopy, that Kv1...
November 23, 2017: Channels
https://www.readbyqxmd.com/read/29168786/effects-of-commonly-used-pesticides-in-china-on-the-mitochondria-and-ubiquitin-proteasome-system-in-parkinson-s-disease
#2
Tingting Chen, Jieqiong Tan, Zhengqing Wan, Yongyi Zou, Henok Kessete Afewerky, Zhuohua Zhang, Tongmei Zhang
Evidence continues to accumulate that pesticides are the leading candidates of environmental toxins that may contribute to the pathogenesis of Parkinson's disease. The mechanisms, however, remain largely unclear. According to epidemiological studies, we selected nine representative pesticides (paraquat, rotenone, chlorpyrifos, pendimethalin, endosulfan, fenpyroximate, tebufenpyrad, trichlorphon and carbaryl) which are commonly used in China and detected the effects of the pesticides on mitochondria and ubiquitin-proteasome system (UPS) function...
November 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29168472/characterization-of-naturally-occurring-pentacyclic-triterpenes-as-novel-inhibitors-of-deubiquitinating-protease-usp7-with-anticancer-activity-in-vitro
#3
Bo Jing, Meng Liu, Li Yang, Hai-Yan Cai, Jie-Bo Chen, Ze-Xi Li, Xi Kou, Yun-Zhao Wu, Dong-Jun Qin, Li Zhou, Jin Jin, Hu Lei, Han-Zhang Xu, Wei-Wei Wang, Ying-Li Wu
Deubiquitinating protease USP7 is a promising therapeutic target for cancer treatment, and interest in developing USP7 inhibitors has greatly increased. In the present study, we reported a series of natural pentacyclic triterpenes with USP7 inhibitory activity in vitro. Among them, both the ursane triterpenes and oleanane triterpenes were more active than the lupine triterpenes, whereas ursolic acid was the most potent with IC50 of 7.0±1.5 μmol/L. Molecular docking studies showed that ursolic acid might occupy the ubiquitin binding pocket of USP7, with the 17-carboxyl group and 3-hydroxyl group playing a vital role in the USP7-ursolic acid interaction...
November 23, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29167802/shutdown-of-interferon-signaling-by-a-viral-hijacked-e3-ubiquitin-ligase
#4
COMMENT
Kaitlin A Davis, John T Patton
Viruses manipulate cellular processes to create an environment favorable to replication. For most viruses, this includes subverting the expression of interferon (IFN), a signaling molecule that can stimulate production of a vast array of antiviral gene products. Rotavirus, a segmented double-stranded RNA virus that causes acute gastroenteritis in infants and young children, inhibits IFN expression through its nonstructural protein NSP1. This viral protein stifles IFN expression by inducing the degradation of host factors that are necessary for upregulating the activity of IFN genes...
November 3, 2017: Microbial Cell
https://www.readbyqxmd.com/read/29167521/dna-methylation-in-silkworm-genome-may-provide-insights-into-epigenetic-regulation-of-response-to-bombyx-mori-cypovirus-infection
#5
Ping Wu, Wencai Jie, Qi Shang, Enoch Annan, Xiaoxu Jiang, Chenxiang Hou, Tao Chen, Xijie Guo
DNA methylation is an important epigenetic modification that regulates a wide range of biological processes including immune response. However, information on the epigenetics-mediated immune mechanisms in insects is limited. Therefore, in this study, we examined transcriptomes and DNA methylomes in the fat body and midgut tissues of silkworm, Bombyx mori with or without B. mori cytoplasmic polyhedrosis virus (BmCPV) infection. The transcriptional profile and the genomic DNA methylation patterns in the midgut and fat body were tissue-specific and dynamically altered after BmCPV challenge...
November 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29167402/the-role-of-cysteine-string-protein-alpha-csp%C3%AE-phosphorylation-at-serine-10-and-34-by-protein-kinase-c%C3%AE-for-presynaptic-maintenance
#6
Toshihiko Shirafuji, Takehiko Ueyama, Naoko Adachi, Ken-Ichi Yoshino, Yusuke Sotomaru, Junsuke Uwada, Azumi Kaneoka, Taro Ueda, Shigeru Tanaka, Izumi Hide, Naoaki Saito, Norio Sakai
Protein Kinase Cγ (PKCγ) knockout (KO) animals exhibit symptoms of Parkinson's disease (PD), including dopaminergic neuronal loss in the substantia nigra. However, the PKCγ substrates responsible for the survival of dopaminergic neurons, in vivo, have not yet been elucidated. Previously, we found 10 potent substrates in the striatum of PKCγ-KO mice. Here, we focused on cysteine string protein alpha (CSPα), one of the proteins from the heat shock protein (HSP) 40 co-chaperone families localized on synaptic vesicles...
November 22, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29167396/targeting-stub1-tissue-factor-axis-normalizes-hyperthrombotic-uremic-phenotype-without-increasing-bleeding-risk
#7
Moshe Shashar, Mostafa E Belghasem, Shinobu Matsuura, Joshua Walker, Sean Richards, Faisal Alousi, Keshab Rijal, Vijaya B Kolachalama, Mercedes Balcells, Minami Odagi, Kazuo Nagasawa, Joel M Henderson, Amitabh Gautam, Richard Rushmore, Jean Francis, Daniel Kirchhofer, Kumaran Kolandaivelu, David H Sherr, Elazer R Edelman, Katya Ravid, Vipul C Chitalia
Chronic kidney disease (CKD/uremia) remains vexing because it increases the risk of atherothrombosis and is also associated with bleeding complications on standard antithrombotic/antiplatelet therapies. Although the associations of indolic uremic solutes and vascular wall proteins [such as tissue factor (TF) and aryl hydrocarbon receptor (AHR)] are being defined, the specific mechanisms that drive the thrombotic and bleeding risks are not fully understood. We now present an indolic solute-specific animal model, which focuses on solute-protein interactions and shows that indolic solutes mediate the hyperthrombotic phenotype across all CKD stages in an AHR- and TF-dependent manner...
November 22, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29167380/self-oligomerization-regulates-stability-of-survival-motor-neuron-smn-protein-isoforms-by-sequestering-an-scf-slmb-degron
#8
Kelsey M Gray, Kevin A Kaifer, David Baillat, Ying Wen, Thomas R Bonacci, Allison D Ebert, Amanda C Raimer, Ashlyn M Spring, Sara Ten Have, Jacqueline J Glascock, Kushol Gupta, Gregory D Van Duyne, Michael J Emanuele, Angus I Lamond, Eric J Wagner, Christian L Lorson, A Gregory Matera
Spinal muscular atrophy (SMA) is caused by homozygous mutations in human SMN1 Expression of a duplicate gene (SMN2) primarily results in skipping of exon 7 and production of an unstable protein isoform, SMNΔ7. Although SMN2 exon skipping is the principal contributor to SMA severity, mechanisms governing stability of SMN isoforms are poorly understood. We used a Drosophila model system and label-free proteomics to identify the SCF(Slmb) ubiquitin E3 ligase complex as a novel SMN binding partner. SCF(Slmb) interacts with a phospho-degron embedded within the human and fruitfly SMN YG-box oligomerization domains...
November 22, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29167343/ubiquitination-of-the-cytoplasmic-domain-of-influenza-a-virus-m2-protein-is-crucial-for-production-of-infectious-virus-particles
#9
Wen-Chi Su, Wen-Ya Yu, Shih-Han Huang, Michael M C Lai
Virus replication is mediated by interactions between virus and host. Here, we demonstrate that influenza A virus membrane protein 2 (M2) can be ubiquitinated. The lysine residue at position 78, which is located in the cytoplasmic domain of M2, is essential for M2 ubiquitination. An M2-K78R (Lys78→Arg78) mutant, which produces ubiquitination-deficient M2, showed a severe defect in production of infectious virus particles. M2-K78R mutant progeny contained more HA proteins, less viral RNAs and less internal viral proteins, including M1 and NP, than the wild-type virus...
November 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29167336/an-insight-into-the-role-of-e3-ubiquitin-ligase-c-cbl-escrt-machinery-and-host-cell-signaling-in-kaposi-s-sarcoma-associated-herpesvirus-kshv-entry-and-trafficking
#10
Binod Kumar, Arunava Roy, Mohanan Valiya Veettil, Bala Chandran
Kaposi's sarcoma-associated herpesvirus (KSHV) in vitro infection of dermal endothelial cell begins with its binding to host cell surface receptor molecules such as heparan sulfate (HS), integrins (α3β1, αVβ3 and αVβ5), xCT and EphA2 receptor tyrosine kinase (EphA2R). These initial events initiate dynamic host protein-protein interactions involving a multi-molecular complex of receptors, signal molecules (FAK, Src, PI3-K, RhoA-GTPase), adaptors (c-Cbl, CIB1, Crk, p130Cas and GEF-C3G), and actin/myosin II light chain that leads to virus entry via macropinocytosis...
November 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29167312/inhibition-of-o-glcnacase-sensitizes-apoptosis-and-reverses-bortezomib-resistance-in-mantle-cell-lymphoma-through-modification-of-truncated-bid
#11
Sudjit Luanpitpong, Nawin Chanthra, Montira Janan, Jirarat Poohadsuan, Parinya Samart, Yaowalak U-Pratya, Yon Rojanasakul, Surapol Issaragrisil
Aberrant energy metabolism represents a hallmark of cancer and contributes to numerous aggressive behaviors of cancer cells, including cell death and survival. Despite the poor prognosis of mantle cell lymphoma (MCL), due to the inevitable development of drug resistance, metabolic reprograming of MCL cells remains an unexplored area. Post-translational modification of proteins via O-GlcNAcylation is an ideal sensor for nutritional changes mediated by O-GlcNAc transferase (OGT) and is removed by O-GlcNAcase (OGA)...
November 22, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29167309/visualizing-the-complex-functions-and-mechanisms-of-the-anaphase-promoting-complex-cyclosome-apc-c
#12
REVIEW
Claudio Alfieri, Suyang Zhang, David Barford
The anaphase promoting complex or cyclosome (APC/C) is a large multi-subunit E3 ubiquitin ligase that orchestrates cell cycle progression by mediating the degradation of important cell cycle regulators. During the two decades since its discovery, much has been learnt concerning its role in recognizing and ubiquitinating specific proteins in a cell-cycle-dependent manner, the mechanisms governing substrate specificity, the catalytic process of assembling polyubiquitin chains on its target proteins, and its regulation by phosphorylation and the spindle assembly checkpoint...
November 2017: Open Biology
https://www.readbyqxmd.com/read/29167269/ring-finger-protein-126-rnf126-suppresses-ionizing-radiation-induced-p53-binding-protein-1-53bp1-foci-formation
#13
Nam Soo Lee, Hae Ryung Chang, Soomi Kim, Jae-Hoon Ji, Joorak Lee, Hyun Ji Lee, Yoojeong Seo, Misun Kang, Joo Seok Han, Kyungjae Myung, Yonghwan Kim, Hongtae Kim
Cells have evolved sophisticated mechanisms to maintain genomic integrity in response to DNA damage. Ionizing radiation (IR) induced DNA damage results in the formation of IR induced foci (iRIF) in the nucleus. The iRIF formation is part of the DNA damage response (DDR), which is an essential signaling cascade that must be strictly regulated because either the loss of or an augmented DDR leads to loss of genome integrity. Accordingly, negative regulation of the DDR is as critical as its activation. In this study, we have identified ring finger protein 126 (RNF126) as a negative regulator of the DDR from a screen of iRIF containing 53BP1...
November 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29166607/kdm2b-regulates-somatic-reprogramming-through-variant-prc1-complex-dependent-function
#14
Zhiwei Zhou, Xuejie Yang, Jiangping He, Jing Liu, Fang Wu, Shengyong Yu, Yuting Liu, Runxia Lin, He Liu, Yuanbin Cui, Chunhua Zhou, Xiaoshan Wang, Jian Wu, Shangtao Cao, Lin Guo, Lihui Lin, Tao Wang, Xiaozhong Peng, Boqing Qiang, Andrew P Hutchins, Duanqing Pei, Jiekai Chen
Polycomb repressive complex 1 (PRC1) plays essential roles in cell-fate determination. Recent studies have found that the composition of mammalian PRC1 is particularly varied and complex; however, little is known about the functional consequences of these variant PRC1 complexes on cell-fate determination. Here, we show that Kdm2b promotes Oct4-induced somatic reprogramming through recruitment of a variant PRC1 complex (PRC1.1) to CpG islands (CGIs). Furthermore, we find that bone morphogenetic protein (BMP) represses Oct4/Kdm2b-induced somatic reprogramming selectively...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29166606/sumoylation-promotes-nuclear-import-and-stabilization-of-polo-like-kinase-1-to-support-its-mitotic-function
#15
Donghua Wen, Jianguo Wu, Lei Wang, Zheng Fu
As a pivotal mitotic regulator, polo-like kinase 1 (PLK1) is under highly coordinated and multi-layered regulation. However, the pathways that control PLK1's activity and function have just begun to be elucidated. PLK1 has recently been shown to be functionally modulated by post-translational modifications (PTMs), including phosphorylation and ubiquitination. Herein, we report that SUMOylation plays an essential role in regulating PLK1's mitotic function. We found that Ubc9 was recruited to PLK1 upon initial phosphorylation and activation by CDK1/cyclin B...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29166018/discovery-of-small-molecule-inhibitors-of-ubiquitin-specific-protease-7-usp7-using-integrated-nmr-and-in-silico-techniques
#16
Paola Di Lello, Richard Pastor, Jeremy M Murray, Robert A Blake, Frederick Cohen, Terry D Crawford, Joy Drobnick, Jason Drummond, Lorna Kategaya, Tracy Kleinheinz, Till Maurer, Lionel Rouge, Xianrui Zhao, Ingrid Wertz, Chudi Ndubaku, Vickie Tsui
USP7 is a deubiquitinase implicated in destabilizing the tumor suppressor p53 and for this reason it has gained increasing attention as a potential oncology target for small molecule inhibitors. Herein we describe the biophysical, biochemical and computational approaches that led to the identification of 4-(2-aminopyridin-3-yl)-phenol compounds described by Kategaya et al.1 as specific inhibitors of USP7. Fragment based lead discovery (FBLD) by NMR combined with virtual screening and re-mining of biochemical high-throughput screening (HTS) hits led to the discovery of a series of ligands that bind in the "palm" region of the catalytic domain of USP7 and inhibit its catalytic activity...
November 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29165588/novel-phosphate-deficiency-responsive-long-non-coding-rnas-in-the-legume-model-plant-medicago-truncatula
#17
Tianzuo Wang, Mingui Zhao, Xiuxiu Zhang, Min Liu, Chenge Yang, Yuhui Chen, Rujin Chen, Jiangqi Wen, Kirankumar S Mysore, Wen-Hao Zhang
Emerging evidence indicates that long non-coding RNAs (lncRNAs) play important roles in the regulation of many biological processes. Inhibition of plant growth due to deficiency in soil inorganic phosphate (Pi) occurs widely across natural and agricultural ecosystems; however, we know little about the function of plant lncRNAs in response to Pi deficiency. To address this issue, we first identified 10 785 lncRNAs in the legume model species Medicago truncatula by sequencing eight strand-specific libraries. Out of these lncRNAs, 358 and 224 were responsive to Pi deficiency in the leaves and roots, respectively...
November 20, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/29165232/functional-analysis-of-the-esab-component-of-the-staphylococcus-aureus-type-vii-secretion-system
#18
M Guillermina Casabona, Grant Buchanan, Martin Zoltner, Catriona P Harkins, Matthew T G Holden, Tracy Palmer
Type VII secretion systems (T7SS) are found in many bacteria and secrete proteins involved in virulence and bacterial competition. In Staphylococcus aureus the small ubiquitin-like EsaB protein has been previously implicated as having a regulatory role in the production of the EsxC substrate. Here we show that in the S. aureus RN6390 strain, EsaB does not genetically regulate production of any T7 substrates or components, but is indispensable for secretion activity. Consistent with EsaB being an essential component of the T7SS, loss of either EsaB or EssC are associated with upregulation of a common set of iron acquisition genes...
November 22, 2017: Microbiology
https://www.readbyqxmd.com/read/29165031/bst2-inhibits-type-i-ifn-interferon-signaling-by-accelerating-mavs-degradation-through-calcoco2-directed-autophagy
#19
Shouheng Jin, Jun Cui
Macroautophagy/autophagy is a conserved lysosomal degradation system that breaks down intracellular material through the formation of double-membrane autophagosomes in eukaryotic cells. Cargo receptors have been illustrated to play essential roles in capturing and delivering specific substrates into phagophores, the precursors to autophagosomes, for degradation. However, the detailed mechanism underlying selective recognition of the substrates for autophagic degradation remains poorly understood. Recently, we have revealed that IFN (interferon)-induced BST2 recruits the E3 ubiquitin ligase MARCH8 to catalyze the K27-linked ubiquitination of MAVS for CALCOCO2-directed autophagic degradation, hence inhibiting DDX58-mediated type I interferon signaling through a negative feedback loop...
November 22, 2017: Autophagy
https://www.readbyqxmd.com/read/29164995/novel-polyubiquitin-imaging-system-polyub-fc-reveals-that-k33-linked-polyubiquitin-is-recruited-by-sqstm1-p62
#20
Yoichi Nibe, Shigeru Oshima, Masanori Kobayashi, Chiaki Maeyashiki, Yu Matsuzawa, Kana Otsubo, Hiroki Matsuda, Emi Aonuma, Yasuhiro Nemoto, Takashi Nagaishi, Ryuichi Okamoto, Kiichiro Tsuchiya, Tetsuya Nakamura, Shinichiro Nakada, Mamoru Watanabe
Ubiquitin chains are formed with 8 structurally and functionally distinct polymers. However, the functions of each polyubiquitin remain poorly understood. We developed a polyubiquitin-mediated fluorescence complementation (PolyUb-FC) assay using Kusabira Green (KG) as a split fluorescent protein. The PolyUb-FC assay has the advantage that monoubiquitination is nonfluorescent and chain-specific poly-ubiquitination can be directly visualized in living cells without using antibodies. We applied the PolyUb-FC assay to examine K33-linked polyubiquitin...
November 22, 2017: Autophagy
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