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https://www.readbyqxmd.com/read/28077314/biological-or-pharmacological-activation-of-protein-kinase-c-alpha-constrains-hepatitis-e-virus-replication
#1
Wenshi Wang, Yijin Wang, Yannick Debing, Xinying Zhou, Yuebang Yin, Lei Xu, Elena Herrera Carrillo, Johannes H Brandsma, Raymond A Poot, Ben Berkhout, Johan Neyts, Maikel P Peppelenbosch, Qiuwei Pan
Although hepatitis E has emerged as a global health issue, there is limited knowledge of its infection biology and no FDA-approved medication is available. Aiming to investigate the role of protein kinases in hepatitis E virus (HEV) infection and to identify potential antiviral targets, we screened a library of pharmacological kinase inhibitors in a cell culture model, a subgenomic HEV replicon containing luciferase reporter. We identified protein kinase C alpha (PKCα) as an essential cell host factor restricting HEV replication...
January 8, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28072404/autophagic-membrane-delivery-through-atg9
#2
Yuchen Feng, Daniel J Klionsky
One of the key questions regarding macroautophagy/autophagy is the mechanism through which the transmembrane protein ATG9 functions in delivering membrane to the expanding phagophore, the sequestering compartment that matures into an autophagosome. In a recent study, Zhou et al. identified a novel mechanism that regulates ATG9 trafficking from the plasma membrane and trans-Golgi network, which involves two conserved sorting signals required for ATG9 interaction with the AP1/2 adaptor complex and phosphorylation of ATG9 at Tyr8 by SRC kinase and at Ser14 by ULK1 for proper function during basal and starvation-induced autophagy...
January 10, 2017: Cell Research
https://www.readbyqxmd.com/read/28055014/globozoospermia-and-lack-of-acrosome-formation-in-gm130-deficient-mice
#3
Feng Han, Chunyi Liu, Lianjun Zhang, Min Chen, Yang Zhou, Yan Qin, Yaqing Wang, Min Chen, Shuguang Duo, Xiuhong Cui, Shilai Bao, Fei Gao
Globozoospermia is a common reproductive disorder that causes male infertility in humans, and the malformation or loss of acrosomes is the prominent feature of this disease. Although the acrosome is thought to be derived from the Golgi apparatus, the detailed molecular mechanisms remain unclear. GM130 is a cis-side localized Golgi matrix protein,whereas the physiological functions of this protein remain elusive. Here we showed that inactivation of GM130-caused male infertility in mouse model. The primary defects were the absence of acrosomes, round sperm heads, and aberrant assembly of the mitochondrial sheath, which comprise the characteristic features of human globozoospermia...
January 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28042029/binding-of-translation-elongation-factors-to-individual-copies-of-the-archaeal-ribosomal-stalk-protein-ap1-assembled-onto-ap0
#4
Takayoshi Honda, Hirotatsu Imai, Takahiro Suzuki, Tomohiro Miyoshi, Kosuke Ito, Toshio Uchiumi
Ribosomes in all organisms contain oligomeric and flexible proteins called stalks, which are responsible for the recruitment of translational GTPase factors to the ribosome. Archaeal ribosomes have three stalk homodimers (aP1)2 that constitute a heptameric complex with the anchor protein aP0. We investigated the factor binding ability of aP1 proteins assembled onto aP0, by gel-retardation assays. The isolated aP0(aP1)2(aP1)2(aP1)2 complex, as well as the form bound to the E. coli 50S core, as a hybrid 50S particle, interacted strongly with elongation factor aEF2, but weakly with aEF1A...
December 29, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28030819/hyperhomocysteinemia-results-from-and-promotes-hepatocellular-carcinoma-via-cyp450-metabolism-by-cyp2j2-dna-methylation
#5
Donghong Zhang, Jinli Lou, Xu Zhang, Lin Zhang, Fei Wang, Danfei Xu, Na Niu, Yidong Wang, Yue Wu, Wei Cui
Hyperhomocysteinemia (HHcy) can result from liver disease or dysfunction and further alters intracellular lipid metabolism. Cytochrome P450 (CYP) arachidonic acid epoxygenases are expressed in human cancers and promote cancer metastasis. This study explored the interaction of Hcy and CYP450 metabolism in hepatocellular carcinoma (HCC). The levels of 4-epoxyeicosatrienoic acid (EET) isomers and their generative enzyme CYP2J2 level as well as intracellular Hcy level were higher in 42 cases of HCC than in paired non-tumor tissue...
December 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/28013423/cloning-expression-profiling-and-promoter-functional-analysis-of-bone-morphogenetic-protein-6-and-7-in-tongue-sole-cynoglossus-semilaevis
#6
Qian Ma, Wenrong Feng, Zhimeng Zhuang, Shufang Liu
Bone morphogenetic proteins (BMPs) play crucial roles in vertebrate developmental process and are associated with the mechanisms which drive early skeletal development. As a first approach to elucidating the role of BMPs in regulating fish bone formation and growth, we describe the cloning, expression profiling and promoter functional analysis of bmp6 and bmp7 in tongue sole (Cynoglossus semilaevis). The full length of bmp6 and bmp7 cDNA sequences is 1939 and 1836 bp, which encodes a protein of 428 and 427 amino acids, respectively...
December 24, 2016: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/28013342/the-tlr4-nos1-ap1-signaling-axis-regulates-macrophage-polarization
#7
Mansi Srivastava, Uzma Saqib, Adnan Naim, Anjali Roy, Dongfang Liu, Deepak Bhatnagar, Ravinder Ravinder, Mirza Saqib Baig
OBJECTIVE: Macrophages polarize to proinflammatory M1 or anti-inflammatory M2 states with distinct physiological functions. This transition within the M1-M2 phenotypes decides the nature, duration and severity of an inflammatory response. Although there is a substantial understanding of the fate of these phenotypes, the underlying molecular mechanism of transition within the M1-M2 phenotypes is not well understood. We have investigated the role of neuronal nitric oxide synthase (NOS1)-mediated regulation of activator protein 1 (AP-1) transcription factor in macrophages as a critical effector of macrophage phenotypic change...
December 24, 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28007961/cjun-dimerization-protein-2-jdp2-is-a-transcriptional-repressor-of-follicle-stimulating-hormone-fsh-%C3%AE-and-is-required-for-preventing-premature-reproductive-senescence-in-female-mice
#8
Carrie R Jonak, Nancy M Lainez, Lacey L Roybal, Alexa D Williamson, Djurdjica Coss
Follicle-stimulating hormone (FSH) regulates follicular growth and stimulates estrogen synthesis in the ovaries. FSH is a heterodimer consisting of an α; subunit, also present in luteinizing hormone, and of a unique β; subunit, which is transcriptionally regulated by gonadotropin releasing hormone 1 (GNRH1). Since most FSH is constitutively secreted, tight transcriptional regulation is critical for maintaining FSH levels within a narrow physiological range. Previously, we reported that GNRH induces FSHβ; transcription via induction of the AP1 transcription factor, a heterodimer of cFos and cJun...
December 22, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28000370/amyloid-precursor-protein-traffics-from-the-golgi-directly-to-early-endosomes-in-an-arl5b-and-ap4-dependent-pathway
#9
Wei Hong Toh, Jing Zhi A Tan, Khalisah L Zulkefli, Fiona J Houghton, Paul A Gleeson
The intracellular trafficking and proteolytic processing of the membrane-bound amyloid precursor protein (APP) are co-ordinated events leading to the generation of pathogenic amyloid-beta (Aβ) peptides. The membrane transport of newly synthesised APP from the Golgi to the endolysosomal system is not well defined, yet is likely to be critical for regulating its processing by β-secretase (BACE1) and γ-secretase. Here we show that the majority of newly synthesised APP is transported from the trans-Golgi network (TGN) directly to early endosomes and then subsequently to the late endosomes/lysosomes with very little transported to the cell surface...
December 20, 2016: Traffic
https://www.readbyqxmd.com/read/27990351/epigenetic-profiling-reveals-a-developmental-decrease-in-promoter-accessibility-during-cortical-maturation-in-vivo
#10
Ishwariya Venkatesh, Matthew T Simpson, Denise M Coley, Murray G Blackmore
Axon regeneration in adult central nervous system (CNS) is limited in part by a developmental decline in the ability of injured neurons to re-express needed regeneration associated genes (RAGs). Adult CNS neurons may lack appropriate pro-regenerative transcription factors, or may display chromatin structure that restricts transcriptional access to RAGs. Here we performed epigenetic profiling around the promoter regions of key RAGs, and found progressive restriction across a time course of cortical maturation...
December 2016: Neuroepigenetics
https://www.readbyqxmd.com/read/27984084/eicosapentaenoic-acid-abolishes-inhibition-of-insulin-induced-mtor-phosphorylation-by-lps-via-ptp1b-downregulation-in-skeletal-muscle
#11
Hong-Kui Wei, Zhao Deng, Shu-Zhong Jiang, Tong-Xing Song, Yuan-Fei Zhou, Jian Peng, Ya-Xiong Tao
Dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) increase insulin signaling in skeletal muscle. In the current study, we investigated the effect of eicosapentaenoic acid (EPA) on insulin-induced mammalian target of rapamycin (mTOR) phosphorylation in myotubes. We showed that EPA did not affect basal and insulin-induced mTOR phosphorylation in myotubes. However, EPA abolished lipopolysaccharide (LPS) -induced deficiency in insulin signaling (P < 0.05). Pre-incubation of nuclear factor κB (NF-κΒ) and c-Jun N-terminal kinases (JNK) inhibitors prevented the decreased insulin-induced mTOR phosphorylation elicited by LPS (P < 0...
October 27, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27934868/regulation-of-matg9-trafficking-by-src-and-ulk1-mediated-phosphorylation-in-basal-and-starvation-induced-autophagy
#12
Changqian Zhou, Kaili Ma, Ruize Gao, Chenglong Mu, Linbo Chen, Qiangqiang Liu, Qian Luo, Du Feng, Yushan Zhu, Quan Chen
Autophagy requires diverse membrane sources and involves membrane trafficking of mATG9, the only membrane protein in the ATG family. However, the molecular regulation of mATG9 trafficking for autophagy initiation remains unclear. Here we identified two conserved classic adaptor protein sorting signals within the cytosolic N-terminus of mATG9, which mediate trafficking of mATG9 from the plasma membrane and trans-Golgi network (TGN) via interaction with the AP1/2 complex. Src phosphorylates mATG9 at Tyr8 to maintain its endocytic and constitutive trafficking in unstressed conditions...
December 9, 2016: Cell Research
https://www.readbyqxmd.com/read/27924160/multivalent-targeting-based-delivery-of-therapeutic-peptide-using-ap1-elp-carrier-for-effective-cancer-therapy
#13
Vijaya Sarangthem, Yunjae Kim, Thoudam Debraj Singh, Bo-Yeon Seo, Sun-Ha Cheon, Young-Jin Lee, Byung-Heon Lee, Rang-Woon Park
Elastin-like polypeptide (ELP)-based drug delivery has been utilized for various applications including cancer therapies for many years. Genetic incorporation of internalization ligands and cell-targeting peptides along with ELP polymer enhanced tumor accumulation and retention time as well as stability and activities of the drug conjugates. Herein, we described a unique delivery system comprised of genetically engineered ELP incorporated with multiple copies of IL-4 receptor targeting peptide (AP1) periodically and proapoptotic peptide (KLAKLAK)2 referred to as AP1-ELP-KLAK...
2016: Theranostics
https://www.readbyqxmd.com/read/27919962/ascorbyl-stearate-promotes-apoptosis-through-intrinsic-mitochondrial-pathway-in-hela-cancer-cells
#14
Shirish D Mane, Maikho Thoh, Deepak Sharma, Santosh K Sandur, K Akhilender Naidu
BACKGROUND: Ascorbic acid is proposed to have antitumor potential against certain cancer types but has the limitation of requiring high doses for treating cancer. Ascorbyl stearate (ASC-S) is a fatty acid ester derivative of ascorbic acid with comparable potent apoptotic activity. The present study was aimed at understanding the pathway involved in apoptotic activity of ASC-S in cervical cancer cells. MATERIALS AND METHODS: The effect of ASC-S on reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) was studied in HeLa cells...
2016: Anticancer Research
https://www.readbyqxmd.com/read/27902472/molecular-mechanism-of-hepatitis-b-virus-hbv-on-suppression-of-raf-kinase-inhibitor-protein-rkip-expression
#15
Xiao-Ke Cheng, Guo-Zheng Yu, Xiao-Dong Li, Xue-Qun Ren
Raf kinase inhibitor protein (RKIP) has been shown to be a suppressor of the mitogen-activated protein kinase pathway and is reported to be involved in human malignancy. However, the molecular mechanism of hepatitis B virus (HBV) in regulating RKIP expression is not yet clarified. In this study, we compared RKIP expression in 107 pairs of matched liver cancer and adjacent non-cancerous liver tissues. Among seven HBV-encoded proteins, we found HBV X (HBX) protein could significantly inhibit the expression level of RKIP, indicating that HBV could suppress RKIP expression through regulating HBX...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27864692/transglutaminase-2-is-involved-in-amyloid-beta1-42-induced-pro-inflammatory-activation-via-ap1-jnk-signalling-pathways-in-thp-1-monocytes
#16
Monica Currò, Chiara Gangemi, Maria Laura Giunta, Nadia Ferlazzo, Michele Navarra, Riccardo Ientile, Daniela Caccamo
Deposition of amyloid-beta (Aβ) peptides has been shown to induce the release of inflammatory factors by activated microglia and brain infiltrating monocytes/macrophages. Interestingly, the enzyme transglutaminase 2 (TG2) has been shown to play a key role in neuroinflammation and regulation of transcription factors involved in immunomodulation. In this study, we aimed to better elucidate the mechanisms underlying TG2 involvement in the pro-inflammatory signaling pathway activated by fibrillar Aβ1-42 in THP-1 monocytes...
November 18, 2016: Amino Acids
https://www.readbyqxmd.com/read/27833998/functional-conservation-and-divergence-of-five-sepallata-like-genes-from-a-basal-eudicot-tree-platanus-acerifolia
#17
Sisi Zhang, Shunjiao Lu, Shuangshuang Yi, Hongji Han, Lei Liu, Jiaqi Zhang, Manzhu Bao, Guofeng Liu
Five SEP -like genes were cloned and identified from Platanus acerifolia through the analysis of expression profiles, protein-protein interaction patterns, and transgenic phenotypes, which suggested that they play conservative and diverse functions in floral initiation and development, fruit development, bud growth, and dormancy. SEPALLATA (SEP) genes have been well characterized in core eudicots and some monocots, and they play important and diverse roles in plant development, including flower meristem initiation, floral organ identity, and fruit development and ripening...
November 11, 2016: Planta
https://www.readbyqxmd.com/read/27815142/spl3-4-5-integrate-developmental-aging-and%C3%A2-photoperiodic-signals-into-the-ft-fd-module-in-arabidopsis-flowering
#18
Jae-Hoon Jung, Hyo-Jun Lee, Jae Yong Ryu, Chung-Mo Park
Environmental sensitivity varies across developmental phases in flowering plants. In the juvenile phase, microRNA156 (miR156)-mediated repression of SQUAMOSA PROMOTER-BINDING PROTEIN-LIKE (SPL) transcription factors renders Arabidopsis plants incompetent to floral inductive signals, including long-day (LD) photoperiod. During the vegetative phase transition, which accompanies a reduction of miR156 and a concomitant elevation of its targets, plants acquire reproductive competence such that LD signals promote flowering...
December 5, 2016: Molecular Plant
https://www.readbyqxmd.com/read/27808010/role-of-neuroinflammation-and-latent-transcription-factors-in-pathogenesis-of-parkinson-s-disease
#19
Rishi Pal, Prafulla Chandra Tiwari, Rajendra Nath, Kamlesh Kumar Pant
Parkinson's disease (PD) the second most common age-associated progressive neurodegenerative disorder is characterized by loss of dopaminergic neurons, cytoplasmic inclusions of aggregated proteins (Lewy bodies), and neuroinflammation. The inflammation of neurons causes release of various inflammatory mediators (IFNs, EGF, IL5, IL6, HGF, LIF and BMP2). The hallmarks of neuroinflammation are the presence of activated microglia and reactive astrocytes in the parenchyma of the CNS and increased production of cytokines, chemokines, prostaglandins, complement cascade proteins, and reactive oxygen and nitrogen species (ROS/RNS) which in some cases can result in disruption of the blood brain barrier and direct participation of the adaptive immune system...
December 2016: Neurological Research
https://www.readbyqxmd.com/read/27787515/ap1-transcription-factors-are-required-to-maintain-the-peripheral-taste-system
#20
Jayasha Shandilya, Yankun Gao, Tapan K Nayak, Stefan G E Roberts, Kathryn F Medler
The sense of taste is used by organisms to achieve the optimal nutritional requirement and avoid potentially toxic compounds. In the oral cavity, taste receptor cells are grouped together in taste buds that are present in specialized taste papillae in the tongue. Taste receptor cells are the cells that detect chemicals in potential food items and transmit that information to gustatory nerves that convey the taste information to the brain. As taste cells are in contact with the external environment, they can be damaged and are routinely replaced throughout an organism's lifetime to maintain functionality...
October 27, 2016: Cell Death & Disease
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