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https://www.readbyqxmd.com/read/29331651/activation-of-p62-keap1-nrf2-antioxidant-pathway-in-the-early-stage-of-acetaminophen-induced-acute-liver-injury-in-mice
#1
Zhenyu Shen, Yu Wang, Zhenhui Su, Ruirui Kou, Keqin Xie, Fuyong Song
Acetaminophen (APAP) overdose can cause severe liver failure even death. Nearly half of drug-induced liver injury is attributed to APAP in the US and many European countries. Oxidative stress has been validated as a critical event involved in APAP-induced liver failure. p62/SQSTM1, a selective autophagy adaptor protein, is reported to regulate Nrf2-ARE antioxidant pathway in response to oxidative stress. However, the exact role of p62-keap1-Nrf2 antioxidant pathway in APAP-induced hepatotoxicity remains unknown...
January 10, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29330417/high-stap1-expression-in-dux4-rearranged-cases-is-not-suitable-as-therapeutic-target-in-pediatric-b-cell-precursor-acute-lymphoblastic-leukemia
#2
Elisabeth M P Steeghs, Marjolein Bakker, Alex Q Hoogkamer, Judith M Boer, Quirine J Hartman, Femke Stalpers, Gabriele Escherich, Valerie de Haas, Hester A de Groot-Kruseman, Rob Pieters, Monique L den Boer
Approximately 25% of the pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cases are genetically unclassified. More thorough elucidation of the pathobiology of these genetically unclassified ('B-other') cases may identify novel treatment options. We analyzed gene expression profiles of 572 pediatric BCP-ALL cases, representing all major ALL subtypes. High expression of STAP1, an adaptor protein downstream of the B-cell receptor (BCR), was identified in BCR-ABL1-like and non-BCR-ABL1-like B-other cases...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330144/kindlin-1-promotes-pulmonary-breast-cancer-metastasis
#3
Sana Sarvi, Hitesh Patel, Jun Li, Georgia L Dodd, Helen Creedon, Morwenna Muir, Jocelyn Ward, John C Dawson, Martin Lee, Jayne Culley, Donald M Salter, Andrew H Sims, Adam Byron, Valerie G Brunton
In breast cancer, increased expression of the cytoskeletal adaptor protein Kindlin-1 has been linked to increased risks of lung metastasis, but the functional basis is unknown. Here we show that in a mouse model of polyomavirus middle T antigen-induced mammary tumorigenesis, loss of Kindlin-1 reduced early pulmonary arrest and later development of lung metastasis. This phenotype relied on the ability of Kindlin-1 to bind and activate β integrin heterodimers. Kindlin-1 loss reduced α4 integrin-mediated adhesion of mammary tumor cells to the adhesion molecule VCAM-1 on endothelial cells...
January 12, 2018: Cancer Research
https://www.readbyqxmd.com/read/29328992/transcriptome-wide-identification-and-competitive-disruption-of-sacum-binding-partners-in-human-colorectal-cancer
#4
Yinguang Zhang, Yongwang Zhang, Yuxiang Zhang
Human sacum is regulatory adaptor protein involved in cellular signaling network of colorectal cancer. Molecular evidences suggest that the protein is integrated into oncogenic signaling network by binding to SH3-containing proteins through its proline-rich motifs. In this study, we have performed a transcriptome-wide analysis and identification of sacum-binding partners in the genome profile of human colorectal cancer. The sacum-binding potency of SH3-containing proteins found in colorectal cancer was investigated by using bioinformatics modeling and intermolecular binding analysis...
December 30, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29328377/feature-genes-in-metastatic-breast-cancer-identified-by-metade-and-svm-classifier-methods
#5
Youlin Tuo, Ning An, Ming Zhang
The aim of the present study was to investigate the feature genes in metastatic breast cancer samples. A total of 5 expression profiles of metastatic breast cancer samples were downloaded from the Gene Expression Omnibus database, which were then analyzed using the MetaQC and MetaDE packages in R language. The feature genes between metastasis and non‑metastasis samples were screened under the threshold of P<0.05. Based on the protein‑protein interactions (PPIs) in the Biological General Repository for Interaction Datasets, Human Protein Reference Database and Biomolecular Interaction Network Database, the PPI network of the feature genes was constructed...
January 9, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29326436/p66shc-deficiency-enhances-cxcr4-and-ccr7-recycling-in-cll-b-cells-by-facilitating-their-dephosphorylation-dependent-release-from-%C3%AE-arrestin-at-early-endosomes
#6
Laura Patrussi, Nagaja Capitani, Francesca Cattaneo, Noemi Manganaro, Alessandra Gamberucci, Federica Frezzato, Veronica Martini, Andrea Visentin, Pier Giuseppe Pelicci, Mario M D'Elios, Livio Trentin, Gianpietro Semenzato, Cosima T Baldari
Neoplastic cell traffic abnormalities are central to the pathogenesis of chronic lymphocytic leukemia (CLL). Enhanced CXC chemokine receptor-4 (CXCR4) and chemokine receptor-7 (CCR7) recycling contributes to the elevated surface levels of these receptors on CLL cells. Here we have addressed the role of p66Shc, a member of the Shc family of protein adaptors the expression of which is defective in CLL cells, in CXCR4/CCR7 recycling. p66Shc reconstitution in CLL cells reduced CXCR4/CCR7 recycling, lowering their surface levels and attenuating B-cell chemotaxis, due to their accumulation in Rab5+ endosomes as serine-phosphoproteins bound to β-arrestin...
January 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29325022/large-scale-exome-datasets-reveal-a-new-class-of-adaptor-related-protein-complex-2-sigma-subunit-ap2%C3%AF-mutations-located-at-the-interface-with-the-ap2-alpha-subunit-that-impair-calcium-sensing-receptor-signalling
#7
Caroline M Gorvin, Raghu Metpally, Victoria J Stokes, Fadil M Hannan, Sarath B Krishnamurthy, John D Overton, Jeffrey G Reid, Gerda E Breitwieser, Rajesh V Thakker
Mutations of the sigma subunit of the heterotetrameric adaptor-related protein complex 2 (AP2σ) impair signalling of the calcium-sensing receptor (CaSR), and cause familial hypocalciuric hypercalcaemia type 3 (FHH3). To date, FHH3-associated AP2σ mutations have only been identified at one residue, Arg15. We hypothesized that additional rare AP2σ variants may also be associated with altered CaSR function and hypercalcaemia, and sought for these by analysing >111,995 exomes (>60,706 from ExAc and dbSNP, and 51,289 from the Geisinger Health System-Regeneron DiscovEHR dataset which also contains clinical data)...
January 9, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29324327/elucidating-the-interfaces-involved-in-card-card-interactions-mediated-by-nlrp1-and-caspase-1-using-molecular-dynamics-simulation
#8
Jitendra Maharana
Inflammasomes are the multi-protein caspase-activating complexes mainly assembled by the sensor proteins (NLRs/ALRs), adaptor molecule (ASC) and effector molecule pro-caspase-1 for the production and release of proinflammatory cytokines, IL-1β and IL-18. NLRP1 is the first NLR known to assemble the multi-protein complex. Unlike NLRP3, NLRP1 has an additional effector binding domain (CARD) at the carboxyl-terminal, which is reported to interact with pro-caspase-1 (precluding the recruitment of ASC) for the transmission of danger signals...
December 24, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29323724/autoregulation-of-rank-ligand-in-oral-squamous-cell-carcinoma-tumor-cells
#9
Yuvaraj Sambandam, Purushoth Ethiraj, Jessica Hathway-Schrader, Chad Novince, Ezhil Panneerselvam, Kumaran Sundaram, Sakamuri V Reddy
Oral squamous cell carcinoma (OSCC) is the most common malignancy among oral cancers and shows potent activity for local bone invasion. Receptor activator of nuclear factor κB (RANK) ligand (RANKL) is critical for bone-resorbing osteoclast formation. We previously demonstrated that OSCC tumor cells express high levels of RANKL. In this study, confocal microscopy demonstrated RANKL specific receptor, RANK expression in OSCC tumor cell lines (SCC1, SCC12 and SCC14a). We also confirmed the expression of RANK and RANKL in primary human OSCC tumor specimens...
January 11, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29323101/actin-filament-associated-protein-1-like-1-mediates-proliferation-and-survival-in-non-small-cell-lung-cancer-cells
#10
Meng Wang, Xingpeng Han, Wei Sun, Xin Li, Guohui Jing, Xun Zhang
BACKGROUND The actin filament-associated protein (AFAP) family consists of 3 novel adaptor proteins: AFAP1, AFAP1L1, and AFAP1L2/XB130. Although evidence shows that AFAP1 and AFAP1L2 play an oncogenic role, the effect of AFAP1L1 on tumor cell behavior has not been fully elucidated, and it remains unknown whether AFAP1L1 could be a prognostic marker and/or therapeutic target of lung cancer. MATERIAL AND METHODS Human A549 non-small cell lung cancer (NSCLC) cells were used in this study. AFAP1L1 gene was knocked down by AFAP1L1 short hairpin RNA (shRNA) transfection...
January 11, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29321312/the-e3-ubiquitin-ligase-siah-1-suppresses-avian-reovirus-infection-by-targeting-p10-for-degradation
#11
Xiang Chen, Zhiyuan He, Mengjiao Fu, Yongqiang Wang, Haiyang Wu, Xiaoqi Li, Hong Cao, Shijun J Zheng
Avian reovirus (ARV) causes viral arthritis, chronic respiratory diseases, retarded growth and malabsorption syndrome. The ARV p10 protein, a viroporin responsible for the induction of cell syncytium formation and apoptosis, is rapidly degraded in host cells. Our previous report demonstrated that the cellular Lysosome Associated Membrane Protein (LAMP)-1 interacted with p10 and was involved in its degradation. However, the molecular mechanism underlying LAMP-1 mediated p10 degradation remains elusive. We report here that E3 ubiquitin ligase Seven in Absentia Homolog (Siah)-1 is critical for p10 ubiquitylation...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29319606/disruption-of-nnos-nos1ap-protein-protein-interactions-suppresses-neuropathic-pain-in-mice
#12
Wan-Hung Lee, Li-Li Li, Aarti Chawla, Andy Hudmon, Yvonne Y Lai, Michael J Courtney, Andrea G Hohmann
Elevated N-methyl-D-aspartate receptor (NMDAR) activity is linked to central sensitization and chronic pain. However, NMDAR antagonists display limited therapeutic potential due to their adverse side effects. Novel approaches targeting the NR2B-PSD95-nNOS complex to disrupt signaling pathways downstream of NMDARs show efficacy in preclinical pain models. Here, we evaluated the involvement of interactions between neuronal nitric oxide synthase (nNOS) and the nitric oxide synthase 1 adaptor protein (NOS1AP) in pronociceptive signaling and neuropathic pain...
January 9, 2018: Pain
https://www.readbyqxmd.com/read/29317286/the-a-enth-domain-containing-protein-ateca4-is-an-adaptor-protein-involved-in-cargo-recycling-from-the-trans-golgi-network-early-endosome-to-the-plasma-membrane
#13
Hong Hanh Nguyen, Myoung Hui Lee, Kyungyoung Song, Gyeongik Ahn, Jihyeong Lee, Inhwan Hwang
Endocytosis and subsequent trafficking pathways are crucial for regulating the activity of plasma membrane-localized proteins. Depending on cellular and physiological conditions, the internalized cargoes are sorted at (and transported from) the trans-Golgi network/early endosome (TGN/EE) to the vacuole for degradation or recycled back to the plasma membrane. How this occurs at the molecular level remains largely elusive. Here we provide evidence that the ENTH domain-containing protein AtECA4 plays a crucial role in recycling cargoes from the TGN/EE to the plasma membrane...
January 6, 2018: Molecular Plant
https://www.readbyqxmd.com/read/29316491/presynaptic-endocytic-factors-in-autophagy-and-neurodegeneration
#14
REVIEW
Domenico Azarnia Tehran, Marijn Kuijpers, Volker Haucke
Neuronal signaling depends on the exocytic fusion and subsequent endocytic retrieval and reformation of neurotransmitter-containing synaptic vesicles at synapses. Recent findings have uncovered surprising roles of presynaptic endocytic proteins in the formation and transport of autophagosomes. These include functions of the membrane remodelling protein endophilin and its downstream effector, the phosphoinositide phosphatase synaptojanin, in autophagosome formation and in Parkinson's disease, the endocytic sorting adaptor CALM in protein degradation via the autophagy/lysosomal pathway in Alzheimer's disease, and the clathrin adaptor complex AP-2 in retrograde transport of signaling autophagosomes to prevent neurodegeneration...
January 6, 2018: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/29312576/matrine-inhibits-bcr-abl-mediated-erk-mapk-pathway-in-human-leukemia-cells
#15
Lingdi Ma, Zhenyu Xu, Jian Wang, Zhichao Zhu, Guibin Lin, Lijia Jiang, Xuzhang Lu, Chang Zou
The BCR/ABL fusion gene and its downstream signaling pathways such as Ras/Raf/MAPK, JAK/STAT3, and PI3K/AKT pathways play important roles in malignant transformation of leukemia, especially chronic myelogenous leukemia (CML). Our previous study showed that matrine, an alkaloid extracted from a Chinese herb radix sophorae, significantly inhibited the proliferation of human CML K562cells, induced cell cycle arrest in G0/G1, and promoted cell apoptosis. In the present study, we investigated the molecular mechanism of matrine in the growth inhibition of leukemia cells using K562 and HL-60 cell lines...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29311275/the-c-terminal-region-of-bacillus-subtilis-swra-is-required-for-activity-and-adaptor-dependent-lona-proteolysis
#16
Anna C Hughes, Sundharraman Subramanian, Charles E Dann, Daniel B Kearns
SwrA is the master activator of flagellar biosynthesis in Bacillus subtilis and SwrA activity is restricted by regulatory proteolysis in liquid environments. SwrA is proteolyzed by the LonA protease but requires a proteolytic adaptor protein, SmiA. Here we show that SwrA and SmiA interact directly. To better understand SwrA activity, SwrA was randomly mutagenized and loss-of-function and gain-of-function mutants were localized primarily to the predicted unstructured C-terminal region. Loss-of-function mutations impaired swarming motility and activation from the Pfla-che promoter...
January 8, 2018: Journal of Bacteriology
https://www.readbyqxmd.com/read/29311151/tks-adaptor-proteins-at-a-glance
#17
REVIEW
Priyanka Saini, Sara A Courtneidge
Tyrosine kinase substrate (Tks) adaptor proteins are considered important regulators of various physiological and/or pathological processes, particularly cell migration and invasion, and cancer progression. These proteins contain PX and SH3 domains, and act as scaffolds, bringing membrane and cellular components in close proximity in structures known as invadopodia or podosomes. Tks proteins, analogous to the related proteins p47phox, p40phox and NoxO1, also facilitate local generation of reactive oxygen species (ROS), which aid in signaling at invadopodia and/or podosomes to promote their activity...
January 8, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29311115/miro-proteins-coordinate-microtubule-and-actin-dependent-mitochondrial-transport-and-distribution
#18
Guillermo López-Doménech, Christian Covill-Cooke, Davor Ivankovic, Els F Halff, David F Sheehan, Rosalind Norkett, Nicol Birsa, Josef T Kittler
In the current model of mitochondrial trafficking, Miro1 and Miro2 Rho-GTPases regulate mitochondrial transport along microtubules by linking mitochondria to kinesin and dynein motors. By generating Miro1/2 double-knockout mouse embryos and single- and double-knockout embryonic fibroblasts, we demonstrate the essential and non-redundant roles of Miro proteins for embryonic development and subcellular mitochondrial distribution. Unexpectedly, the TRAK1 and TRAK2 motor protein adaptors can still localise to the outer mitochondrial membrane to drive anterograde mitochondrial motility in Miro1/2 double-knockout cells...
January 8, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29306018/aldehyde-dehydrogenase-1a3-aldh1a3-is-regulated-by-autophagy-in-human-glioblastoma-cells
#19
Wei Wu, Johannes Schecker, Sylvia Würstle, Fabian Schneider, Martin Schönfelder, Jürgen Schlegel
Aldehyde dehydrogenase is a polymorphic enzyme, which responsible for the oxidation of aldehydes. It has been shown that ALDH1A3 is expressed in human glioblastomas and that its expression correlates with a worse prognosis. In our present study ALDH1A3 expression was associated with resistance against Temozolomide (TMZ) treatment and sensitivity could be re-established in ALDH1A3 knockout cells. TMZ treatment at high concentrations diminished ALDH1A3 protein and this downregulation made the tumor cells more sensitive to chemotherapy...
January 3, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29305295/the-hippo-pathway-in-normal-development-and-cancer
#20
REVIEW
Marcello Maugeri-Saccà, Ruggero De Maria
The Hippo pathway is a central regulator of organ size and tissue homeostasis. Hippo kinases and adaptor proteins mediate the phosphorylation and inactivation of YAP and TAZ, two closely related transcription co-activators. The Hippo pathway responds to a variety of extracellular and intracellular signals, spanning from cell-cell contact and mechanical cues to ligands of G-protein-coupled receptors and metabolic avenues. In some instances, YAP/TAZ activation is tuned by forces that bypass the Hippo kinase module, adding further complexity to the biology of the pathway...
January 2, 2018: Pharmacology & Therapeutics
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