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https://www.readbyqxmd.com/read/29149649/chk1-inhibitors-overcome-imatinib-resistance-in-chronic-myeloid-leukemia-cells
#1
Hu Lei, Jin Jin, Meng Liu, Xiangyun Li, Hao Luo, Li Yang, Hanzhang Xu, Yingli Wu
Drug resistance to tyrosine kinase inhibitors (TKIs) is currently a clinical problem of chronic myelogenous leukemia (CML). Bcr-Abl protein depletion is considered as a way to overcome drug resistance to TKIs. In our study, Chk1 inhibitors, AZD7762 and MK-8776, had strong antitumor effects on CML cell line KBM5 and imatinib-resistant form KBM5(T315I). Moreover, Chk1 inhibitors showed a strong cytotoxic effect on leukemia cells from primary CML and imatinib-resistance CML patients, but low cytotoxic effect on normal human mononuclear cells...
November 11, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29149643/the-role-of-the-p38-activated-protein-kinase-signaling-pathway-mediated-autophagy-in-cadmium-exposed-monogonont-rotifer-brachious-koreanus
#2
Hye-Min Kang, Chang-Bum Jeong, Min-Sub Kim, Jin-Sol Lee, Jiaying Zhou, Young Hwan Lee, Duck-Hyun Kim, Eunyoung Moon, Hee-Seok Kweon, Su-Jae Lee, Jae-Seong Lee
Autophagy is a 'self-eating' system that regulates the degradation of cellular components and is involved in various biological processes including survival and development. However, despite its crucial role in organisms, the regulatory mechanism of autophagy remains largely unclear, particularly in invertebrates. In this study, conserved autophagy in the rotifer Brachionus koreanus in response to cadmium (Cd) exposure was verified by measuring acidic vesicle organelles using acridine orange (AO) and neutral red (NR) staining, and by detecting LC3 I/II on Western blot and immunofluorescence...
November 10, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/29149631/prostaglandin-j2-promotes-o-glcnacylation-raising-app-processing-by-%C3%AE-and-%C3%AE-secretases-relevance-to-alzheimer-s-disease
#3
Teneka Jean-Louis, Patricia Rockwell, Maria E Figueiredo-Pereira
Regulation of the amyloid precursor protein (APP) processing by α- and β-secretases is of special interest to Alzheimer's disease (AD), as these proteases prevent or mediate amyloid beta formation, respectively. Neuroinflammation is also implicated in AD. Our data demonstrate that the endogenous mediator of inflammation prostaglandin J2 (PGJ2) promotes full-length APP (FL-APP) processing by α- and β-secretases. The decrease in FL-APP was independent of proteasomal, lysosomal, calpain, caspase, and γ-secretase activities...
November 14, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29149599/autophagosomal-content-profiling-reveals-an-lc3c-dependent-piecemeal-mitophagy-pathway
#4
François Le Guerroué, Franziska Eck, Jennifer Jung, Tatjana Starzetz, Michel Mittelbronn, Manuel Kaulich, Christian Behrends
Autophagy allows the degradation of cytosolic endogenous and exogenous material in the lysosome. Substrates are engulfed by double-membrane vesicles, coined autophagosomes, which subsequently fuse with lysosomes. Depending on the involvement of specific receptor proteins, autophagy occurs in a selective or nonselective manner. While this process is well understood at the level of bulky cargo such as mitochondria and bacteria, we know very little about individual proteins and protein complexes that are engulfed and degraded by autophagy...
November 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29149406/role-and-fate-of-tctp-in-protein-degradative-pathways
#5
Michel Vidal
This chapter focuses on published studies specifically concerning TCTP and its involvement in degradation or stabilization of various proteins, and also in its own degradation in different ways. The first part relates to the inhibition of proteasomal degradation of proteins. This can be achieved by masking ubiquitination sites of specific partners, by favoring ubiquitin E3 ligase degradation, or by regulating proteasome activity. The second part addresses the ability of TCTP to favor degradation of specific proteins through proteasome or macroautophagic pathways...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29149173/trade-off-and-flexibility-in-the-dynamic-regulation-of-the-cullin-ring-ubiquitin-ligase-repertoire
#6
Ronny Straube, Meera Shah, Dietrich Flockerzi, Dieter A Wolf
Cullin-RING ubiquitin ligases (CRLs) catalyze the ubiquitylation of substrates many of which are degraded by the 26S proteasome. Their modular architecture enables recognition of numerous substrates via exchangeable substrate receptors that competitively bind to a cullin scaffold with high affinity. Due to the plasticity of these interactions there is ongoing uncertainty how cells maintain a flexible CRL repertoire in view of changing substrate loads. Based on a series of in vivo and in vitro studies, different groups proposed that the exchange of substrate receptors is mediated by a protein exchange factor named Cand1...
November 17, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/29149107/treponema-denticola-chymotrypsin-like-proteinase-may-contribute-to-orodigestive-carcinogenesis-through-immunomodulation
#7
Mikko T Nieminen, Dyah Listyarifah, Jaana Hagström, Caj Haglund, Daniel Grenier, Dan Nordström, Veli-Jukka Uitto, Marcela Hernandez, Tülay Yucel-Lindberg, Taina Tervahartiala, Mari Ainola, Timo Sorsa
BACKGROUND: Periodontal pathogens have been linked to oral and gastrointestinal (orodigestive) carcinogenesis. However, the exact mechanisms remain unknown. Treponema denticola (Td) is associated with severe periodontitis, a chronic inflammatory disease leading to tooth loss. The anaerobic spirochete Td is an invasive bacteria due to its major virulence factor chymotrypsin-like proteinase. Here we aimed to investigate the presence of Td chymotrypsin-like proteinase (Td-CTLP) in major orodigestive tumours and to elucidate potential mechanisms for Td to contribute to carcinogenesis...
November 16, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29149056/characterization-of-ovine-a3z1-restriction-properties-against-small-ruminant-lentiviruses-srlvs
#8
Lorena de Pablo-Maiso, Idoia Glaria, Helena Crespo, Estanislao Nistal-Villán, Valgerdur Andrésdóttir, Damián de Andrés, Beatriz Amorena, Ramsés Reina
Intrinsic factors of the innate immune system include the apolipoprotein B editing enzyme catalytic polypeptide-like 3 (APOBEC3) protein family. APOBEC3 inhibits replication of different virus families by cytosine deamination of viral DNA and a not fully characterized cytosine deamination-independent mechanism. Sheep are susceptible to small ruminant lentivirus (SRLVs) infection and contain three APOBEC3 genes encoding four proteins (A3Z1, Z2, Z3 and Z2-Z3) with yet not deeply described antiviral properties...
November 17, 2017: Viruses
https://www.readbyqxmd.com/read/29148898/enhancement-of-invadopodia-activity-in-glioma-cells-by-sublethal-doses-of-irradiation-and-temozolomide
#9
Leon Mao, Clarissa A Whitehead, Lucia Paradiso, Andrew H Kaye, Andrew P Morokoff, Rodney B Luwor, Stanley S Stylli
OBJECTIVE Glioblastoma is the most common primary central nervous system tumor in adults. These tumors are highly invasive and infiltrative and result in tumor recurrence as well as an extremely poor patient prognosis. The current standard of care involves surgery, radiotherapy, and chemotherapy. However, previous studies have suggested that glioblastoma cells that survive treatment are potentially more invasive. The goal of this study was to investigate whether this increased phenotype in surviving cells is facilitated by actin-rich, membrane-based structures known as invadopodia...
November 17, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/29148754/eurycomalactone-inhibits-expression-of-endothelial-adhesion-molecules-at-a-post-transcriptional-level
#10
Clemens Malainer, Daniel Schachner, Enrico Sangiovanni, Atanas G Atanasov, Stefan Schwaiger, Hermann Stuppner, Elke H Heiss, Verena M Dirsch
The C-19 quassinoid eurycomalactone (1) has recently been shown to be a potent (IC50 = 0.5 μM) NF-κB inhibitor in a luciferase reporter model. In this study, we show that 1 with similar potency inhibited the expression of the NF-κB-dependent target genes ICAM-1, VCAM-1, and E-selectin in TNFα-activated human endothelial cells (HUVECtert) by flow cytometry experiments. Surprisingly, 1 (2 μM) did not inhibit TNFα-induced IKKα/β or IκBα phosphorylation significantly. Also, the TNFα-induced degradation of IκBα remained unchanged in response to 1 (2 μM)...
November 17, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/29148061/endocannabinoids-modulate-gq-11-protein-coupled-receptor-agonist-induced-vasoconstriction-via-a-negative-feedback-mechanism
#11
REVIEW
Olga Karpińska, Marta Baranowska-Kuczko, Monika Kloza, Hanna Kozłowska
OBJECTIVES: The endocannabinoid (eCB) system centrally and peripherally regulates cardiovascular parameters, including blood pressure, in health and disease. The relationship between Gq/11 protein-coupled receptor activation, regulation of eCBs release (mainly 2-arachidonoylglycerol) and subsequent CB1 receptor activation was initially observed in the central nervous system. Here, we review the latest findings from systemic physiological studies which include for the first time data from pulmonary arteries...
November 17, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/29147907/protein-repair-from-glycation-by-glyoxals-by-the-dj-1-family-maillard-deglycases
#12
Mouadh Mihoub, Jad Abdallah, Gilbert Richarme
DJ-1 and its prokaryotic homologs, Hsp31, YhbO and YajL from Escherichia coli and PfpI from Pyrococcus furiosus, repair proteins from glycation by glyoxals (R-CO-CHO), which constitute their major glycating agents. Glycation is a non-enzymatic covalent reaction discovered by Louis Camille Maillard in 1912, between reactive carbonyls (reducing sugars and glyoxals) and amino acids (cysteine, arginine and lysine), which inactivates proteins. By degrading Maillard adducts formed between carbonyls and thiols or amino groups, the DJ-1 family Maillard deglycases prevent the formation of the so-called advanced glycation end products (AGEs) that arise from Maillard adducts after dehydrations, oxidations and rearrangements...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29147904/the-multifaceted-roles-of-dj-1-as-an-antioxidant
#13
Prahlad V Raninga, Giovanna Di Trapani, Kathryn F Tonissen
The DJ-1 protein was originally linked with Parkinson's disease and is now known to have antioxidant functions. The protein has three redox-sensitive cysteine residues, which are involved in its dimerisation and functional properties. A mildly oxidised form of DJ-1 is the most active form and protects cells from oxidative stress conditions. DJ-1 functions as an antioxidant through a variety of mechanisms, including a weak direct antioxidant activity by scavenging reactive oxygen species. DJ-1 also regulates a number of signalling pathways, including the inhibition of apoptosis signal-regulating kinase 1 (ASK1)-induced apoptosis under oxidative stress conditions...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29147820/cue-signal-response-analysis-in-3d-chondrocyte-scaffolds-with-anabolic-stimuli
#14
Michael Neidlin, Antonion Korcari, Giorgos Macheras, Leonidas G Alexopoulos
Articular cartilage is an avascular connective tissue responsible for bearing loads. Cell signaling plays a central role in cartilage homeostasis and tissue engineering by directing chondrocytes to synthesize/degrade the extracellular matrix or promote inflammatory responses. The aim of this paper was to investigate anabolic, catabolic and inflammatory pathways of well-known and underreported anabolic stimuli in 3D chondrocyte cultures and connect them to diverse cartilage responses including matrix regeneration and cell communication...
November 16, 2017: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/29147811/c-terminal-region-of-human-p53-attenuates-buffalo-p53%C3%A2-n-terminal-specific-transactivation-of-p21-promoter-by-modulating-tetramerization-of-the-protein
#15
Minu Singh, Tapas Mukhopadhyay
Here, we have studied in p53 null H1299 lung carcinoma cells, the dominant-negative effect of human p53 (h-p53) on buffalo p53 (b-p53) induced nuclear transactivation-dependent function. Recently, we have isolated and cloned the full-length cDNA of buffalo p53. Buffalo and human p53 proteins exhibit a high degree of structural and functional similarities. In transiently transfected H1299 cell line b-p53 appeared to be more sensitive to Mdm2-mediated degradation as compared to h-p53, although its ability to transactivate p21 promoter was stronger than that of the human counterpart...
November 16, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29147094/physicochemical-properties-of-gelatin-extracted-from-buffalo-hide-pretreated-with-different-acids
#16
Sri Mulyani, Francis M C Sigit Setyabudi, Yudi Pranoto, Umar Santoso
The acid pretreatment of collagen molecules disrupts their crosslinks and assists in the release of acid-soluble proteins, fats, and other components. Generally, to achieve optimum extraction efficiency, strong acids may be used at a lower acid concentration compared to weak acids. This study aimed to determine the yield and physicochemical properties of gelatins extracted from buffalo hides pretreated with different acids. Hides were extracted with hydrochloric, citric, and acetic acids at concentrations of 0...
2017: Korean Journal for Food Science of Animal Resources
https://www.readbyqxmd.com/read/29146937/tfeb-regulates-lysosomal-positioning-by-modulating-tmem55b-expression-and-jip4-recruitment-to-lysosomes
#17
Rose Willett, José A Martina, James P Zewe, Rachel Wills, Gerald R V Hammond, Rosa Puertollano
Lysosomal distribution is linked to the role of lysosomes in many cellular functions, including autophagosome degradation, cholesterol homeostasis, antigen presentation, and cell invasion. Alterations in lysosomal positioning contribute to different human pathologies, such as cancer, neurodegeneration, and lysosomal storage diseases. Here we report the identification of a novel mechanism of lysosomal trafficking regulation. We found that the lysosomal transmembrane protein TMEM55B recruits JIP4 to the lysosomal surface, inducing dynein-dependent transport of lysosomes toward the microtubules minus-end...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29146913/autophagy-acts-through-traf3-and-relb-to-regulate-gene-expression-via-antagonism-of-smad-proteins
#18
Alice C Newman, Alain J Kemp, Yvette Drabsch, Christian Behrends, Simon Wilkinson
Macroautophagy can regulate cell signalling and tumorigenesis via elusive molecular mechanisms. We establish a RAS mutant cancer cell model where the autophagy gene ATG5 is dispensable in A549 cells in vitro, yet promotes tumorigenesis in mice. ATG5 represses transcriptional activation by the TGFβ-SMAD gene regulatory pathway. However, autophagy does not terminate cytosolic signal transduction by TGFβ. Instead, we use proteomics to identify selective degradation of the signalling scaffold TRAF3. TRAF3 autophagy is driven by RAS and results in activation of the NF-κB family member RELB...
November 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29146855/draft-genome-sequence-of-entomopathogenic-brevibacillus-laterosporus-strain-lak-1210-an-alkaliphilic-chitin-degrader
#19
Lakshmi Prasanna, Tushar Ranjan Moharana, Nizamuddin Sheikh, Veerabhadra Rao Arravapalli, Thangaraj Kumaraswamy, Vincent G H Eijsink, Madhusudhana Rao Nalam
We announce here the draft genome sequence of Brevibacillus laterosporus strain Lak 1210, isolated from mangrove soil. This alkaliphilic strain is an efficient chitin degrader and has the ability to control insects and inhibit phytopathogenic fungi. The assembly consists of 5,082,926 bp, with 4,321 protein-coding sequences and a GC content of 41.15%.
November 16, 2017: Genome Announcements
https://www.readbyqxmd.com/read/29146236/infectious-bursal-disease-virus-protein-vp4-suppresses-type-i-interferon-expression-via-inhibiting-k48-linked-ubiquitylation-of-glucocorticoid-induced-leucine-zipper-gilz
#20
Zhiyuan He, Xiang Chen, Mengjiao Fu, Jun Tang, Xiaoqi Li, Hong Cao, Yongqiang Wang, Shijun J Zheng
Viruses have developed a variety of methods to evade host immune response. Our previous study showed that infectious bursal disease virus (IBDV) inhibited type I interferon production via interaction of VP4 with cellular glucocorticoid-induced leucine zipper (GILZ) protein. However, the exact underlying molecular mechanism is still unclear. In this study, we found that IBDV VP4 suppressed GILZ degradation by inhibiting K48-linked ubiquitylation of GILZ. Furthermore, mutation of VP4 (R41G) abolished the inhibitory effect of VP4 on IFN-β expression and GILZ ubiquitylation, indicating that the amino acid 41R of VP4 was required for the suppression of IFN-β expression and GILZ ubiquitylation...
October 28, 2017: Immunobiology
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