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Numb protein

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https://www.readbyqxmd.com/read/29217616/interactome-mapping-uncovers-a-general-role-for-numb-in-protein-kinase-regulation
#1
Ran Wei, Tomonori Kaneko, Xuguang Liu, Huadong Liu, Lei Li, Courtney Voss, Eric Liu, Ningning He, Shawn S C Li
Cellular functions are frequently regulated by protein-protein interactions involving the binding of a modular domain in one protein to a specific peptide sequence in another.  This mechanism may be explored to identify binding partners for proteins harboring a peptide-recognition domain. Here we report a proteomic strategy combining peptide and protein microarray screening with biochemical and cellular assays to identify modular domain-mediated protein-protein interactions in a systematic manner. We applied this strategy to Numb, a multi-functional protein containing a phosphotyrosine-binding (PTB) domain...
December 7, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29201206/combined-treatment-of-diabetic-nephropathy-with-alprostadil-and-calcium-dobesilate
#2
Lili Qin, Wenjun Qin, Jianfei Wang, Lin Lin
This study investigated the effects of alprostadil combined with calcium dobesilate on the treatment of diabetic nephropathy. We recruited 80 patients with diabetic nephropathy, who were randomly divided into experimental (n=40) and control (n=40) groups. Patients received high-quality low-protein diabetic diet intervention and subcutaneous injection of insulin to adjust blood glucose, combined with antihypertensive, antiplatelet drugs, and other comprehensive treatments. The control group received alprostadil and the experimental group received alprostadil combined with calcium dobesilate...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29198941/hypoxic-induction-of-vasorin-regulates-notch1-turnover-to-maintain-glioma-stem-like-cells
#3
Jianghong Man, Xingjiang Yu, Haidong Huang, Wenchao Zhou, Chaomei Xiang, Haohao Huang, Lucio Miele, Zhenggang Liu, Gurkan Bebek, Shideng Bao, Jennifer S Yu
Tumor hypoxia is associated with poor patient survival and is a characteristic of glioblastoma. Notch signaling is implicated in maintaining glioma stem-like cells (GSCs) within the hypoxic niche, although the molecular mechanisms linking hypoxia to Notch activation have not been clearly delineated. Here we show that Vasorin is a critical link between hypoxia and Notch signaling in GSCs. Vasorin is preferentially induced in GSCs by a HIF1α/STAT3 co-activator complex and stabilizes Notch1 protein at the cell membrane...
November 23, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29190716/suppression-of-cancer-stemness-by-upregulating-ligand-of-numb-protein-x1-in-colorectal-carcinoma
#4
Lin Ma, Lan Wang, Yating Shan, Muhammad Nafees, Elshoura Ihab, Ruhui Zhang, Fangjun Wang, Wu Yin
Cancer stem-like cells (CSCs) have been reported to play major roles in tumorigenesis, tumor relapse, and metastasis after therapy against colorectal carcinoma (CRC). Therefore, identification of colorectal CSC regulators could provide promising targets for CRC. Ligand-of-Numb protein X1 (LNX1) is one E3 ubiquitin ligase which mediates the ubiquitination and degradation of Numb. Although several studies indicate LNX1 could be a potential suppressor of cancer diseases, the functions of LNX1 in mediating cancer stemness remain poorly understood...
2017: PloS One
https://www.readbyqxmd.com/read/29176823/vitamin-d-receptor-is-present-on-the-neuronal-plasma-membrane-and-is-co-localized-with-amyloid-precursor-protein-adam10-or-nicastrin
#5
Erdinç Dursun, Duygu Gezen-Ak
Our recent study indicated that vitamin D and its receptors are important parts of the amyloid processing pathway in neurons. Yet the role of vitamin D receptor (VDR) in amyloid pathogenesis is complex and all regulations over the production of amyloid beta cannot be explained solely with the transcriptional regulatory properties of VDR. Given that we hypothesized that VDR might exist on the neuronal plasma membrane in close proximity with amyloid precursor protein (APP) and secretase complexes. The present study primarily focused on the localization of VDR in neurons and its interaction with amyloid pathology-related proteins...
2017: PloS One
https://www.readbyqxmd.com/read/29121065/proteomic-analysis-reveals-novel-ligands-and-substrates-for-lnx1-e3-ubiquitin-ligase
#6
Joan A Lenihan, Orthis Saha, Paul W Young
Ligand of Numb protein X1 (LNX1) is an E3 ubiquitin ligase that contains a catalytic RING (Really Interesting New Gene) domain and four PDZ (PSD-95, DlgA, ZO-1) domains. LNX1 can ubiquitinate Numb, as well as a number of other ligands. However, the physiological relevance of these interactions in vivo remain unclear. To gain functional insights into the LNX family, we have characterised the LNX1 interactome using affinity purification and mass spectrometry. This approach identified a large number of novel LNX1-interacting proteins, as well as confirming known interactions with NUMB and ERC2...
2017: PloS One
https://www.readbyqxmd.com/read/29115587/anticancer-effect-of-quinacrine-on-diffuse-large-b%C3%A2-cell-lymphoma-via-inhibition-of-msi2%C3%A2-numb-signaling-pathway
#7
Shujun Yang, Lixia Sheng, Kaihong Xu, Yi Wang, Huiling Zhu, Ping Zhang, Qitian Mu, Guifang Ouyang
Diffuse large B‑cell lymphoma (DLBCL) is the most common subtype of non‑Hodgkin's lymphoma. Despite improvements in the clinical outcomes of DLBCL, ~30% of patients will develop relapse/refractory disease. Therefore, novel therapeutic drugs have been investigated to improve disease outcomes. Previous studies have revealed the anticancer effects of quinacrine (QC) on tumor cells in vitro, although its role in human DLBCL is yet to be identified. The present study sought to examine the cytotoxic effect of QC on DLBCL cells...
October 26, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29113155/poems-syndrome-presentation-with-progressive-weakness-in-upper-and-lower-limbs-a-case-report
#8
Chuang-Jie Cao, Cheng-Yun Dou, Ke-Hua Zhou, Jin-Bo Liu, Hong Lai
Polyneuropathy, organomegaly, endocrinopathy, M proteins, and skin changes (POEMS) syndrome is a rare variant of plasma cell disorders with multiple systemic manifestations. A 50-year-old female patient presented with progressive weakness in her upper and lower limbs; tingling, numbness and burning in her feet; polyneuropathy (demyelinating in the majority of cases of POEMS syndrome); monoclonal plasma cell disorder (typicallyλ-restricted in cases of POEMS syndrome); sclerotic lesions on the spine and pelvis; organomegaly, including hepatomegaly, splenomegaly and lymphadenopathy; edema; pleural effusion; adrenal, thyroidal, pituitary, gonadal and pancreatic endocrinopathy; skin changes, including hyperpigmentation, dry skin and hypertrichosis; thrombocytosis; pulmonary hypertension; low vitamin B12 and weight loss...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29108667/clinical-electrophysiological-genetic-and-imaging-features-of-six-chinese-han-patients-with-hereditary-neuropathy-with-liability-to-pressure-palsies-hnpp
#9
Bin Chen, Songtao Niu, Xingao Wang, Wei Li, Na Chen, Zaiqiang Zhang
Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant peripheral neuropathy caused by mutations in the peripheral myelin protein 22 (PMP22) gene. This study summarizes the clinical, electrophysiological, genetic, and imaging features of six unrelated Chinese Han patients with HNPP. Age of onset was within the second decade in five patients, and 46 years of age in one patient. Weakness or numbness in a unilateral lower extremity was the most common symptom in 5 patients, and bilateral sensorineural hearing loss was also detected in one patient...
November 3, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/29078790/hereditary-neuropathy-with-liability-to-pressure-palsy-hnpp-report-of-a-family-with-a-new-point-mutation-in-pmp22-gene
#10
Carlo Fusco, Carlotta Spagnoli, Grazia Gabriella Salerno, Elena Pavlidis, Daniele Frattini, Francesco Pisani
BACKGROUND: Hereditary neuropathy with liability to pressure palsy (HNPP) is an autosomal dominant disorder most commonly presenting with acute-onset, non-painful focal sensory and motor mononeuropathy. Approximately 80% of patients carry a 1.5 Mb deletion of chromosome 17p11.2 involving the peripheral myelin protein 22 gene (PMP22), the same duplicated in Charcot-Marie-Tooth 1A patients. In a small proportion of patients the disease is caused by PMP22 point mutations. CASE PRESENTATION: We report on a familial case harbouring a new point mutation in the PMP22 gene...
October 27, 2017: Italian Journal of Pediatrics
https://www.readbyqxmd.com/read/29066856/modelling-acrylamide-acute-neurotoxicity-in-zebrafish-larvae
#11
Eva Prats, Cristian Gómez-Canela, Shani Ben-Lulu, Tamar Ziv, Francesc Padrós, Daniel Tornero, Natàlia Garcia-Reyero, Romà Tauler, Arie Admon, Demetrio Raldúa
Acrylamide (ACR), a type-2 alkene, may lead to a synaptopathy characterized by ataxia, skeletal muscles weakness and numbness of the extremities in exposed human and laboratory animals. Currently, only the mildly affected patients undergo complete recovery, and identification of new molecules with therapeutic bioactivity against ACR acute neurotoxicity is urgently needed. Here, we have generated a zebrafish model for ACR neurotoxicity by exposing 5 days post-fertilization zebrafish larvae to 1 mM ACR for 3 days...
October 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29063319/pattern-of-notch2-numb-and-cas8-gene-expression-in-relevant-structures-of-the-rat-brain-during-formation-of-spatial-memory
#12
M A Gruden', Z I Storozheva, A M Ratmirov, V V Sherstnev
The expression of Notch2, Numb, and Cas8 genes, whose protein products are involved in regulation of neurogenesis/neuroapoptosis processes, was studied in the relevant cerebral structures of male Wistar rats trained in a spatial habit. The formation of long-term spatial memory was found to be associated with the formation of a specific pattern of transcription activity of the studied genes in different brain structures. The maximum expression of Notch2 gene was found in the hippocampus and cerebellum, the maximum expression of Numb was detected in the prefrontal cortex and cerebellum, and the maximum expression of Cas8 was revealed in the prefrontal cortex of trained animals...
October 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29056006/-mechanism-of-astragaloside-prevents-cholestatic-liver-fibrosis-through-inhibition-of-notch-signaling-activation
#13
Y P Mu, X Zhang, W W Fan, X W Li, G F Chen, J M Chen, H Zhang, P Liu
Objective: The Notch signaling pathway is closely related to biliary fibrosis. Previous studies have shown that Astragaloside (AS) can prevent the progression of cholestatic liver fibrosis. The purpose of this study is to observe the effect of AS on the regulation of Notch signaling pathway in biliary fibrosis. Methods: Cholestatic liver fibrosis was established by common bile duct ligation (BDL) in rats. Two weeks after BDL, the rats were randomly divided into a model group (i.e., BDL), an Astragalosides group (AS), and a sorafenib (SORA) positive control group and treated for 3 weeks...
August 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/29042443/mammalian-numb-protein-antagonizes-notch-by-controlling-postendocytic-trafficking-of-the-notch-ligand-delta-like-4
#14
Ximing Shao, Zhihao Ding, Ming Zhao, Ke Liu, Haiyan Sun, Juntao Chen, Xianming Liu, Yuzhen Zhang, Yang Hong, Huashun Li, Hongchang Li
The biological antagonism between the signaling proteins Numb and Notch has been implicated in the regulation of many developmental processes, especially in asymmetric cell division. Mechanistic studies show that Numb inactivates Notch via endocytosis and proteasomal degradation that directly reduce Notch protein levels at the cell surface. However, some aspects of how Numb antagonizes Notch remain unclear. Here, we report a novel mechanism in which Numb acts as a Notch antagonist by controlling the intracellular destination and stability of the Notch ligand Delta-like 4 (Dll4) through a postendocytic-sorting process...
October 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28974699/numbl-interacts-with-tak1-traf6-and-nemo-to-negatively-regulate-nf-%C3%AE%C2%BAb-signaling-during-osteoclastogenesis
#15
Gaurav Swarnkar, Tim Hung-Po Chen, Manoj Arra, Amjad M Nasir, Gabriel Mbalaviele, Yousef Abu-Amer
NF-κB signaling is essential for osteoclast differentiation and skeletal homeostasis. We have reported recently that NUMB-like (NUMBL) protein modulates osteoclastogenesis by down regulating NF-κB activation. Herein, we decipher the mechanism underlying this phenomenon. We found that whereas NUMBL mRNA expression decreases upon stimulation of wild type (WT) bone marrow macrophages (BMMs) with RANKL, TAK1 deficiency in these cells leads to increased NUMBL and decreased TRAF6 and NEMO expression. These changes were restored upon WT-TAK1 expression, but not with catalytically inactive TAK1-K63W, suggesting that TAK1 enzymatic activity is required for these events...
October 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28871126/mdm2-contributes-to-high-glucose-induced-glomerular-mesangial-cell-proliferation-and-extracellular-matrix-accumulation-via-notch1
#16
Chun-Tao Lei, Hui Tang, Chen Ye, Chao-Qun You, Jiao Zhang, Chun-Yun Zhang, Wei Xiong, Hua Su, Chun Zhang
Murine double minute 2 (MDM2) is an E3-ubiquitin ligase critical for various biological functions. Previous data have revealed an indispensable role of MDM2 in kidney homeostasis. However, its role in glomerular mesangial cell (GMC) proliferation and extracellular matrix (ECM) accumulation during hyperglycemia condition remains unclear. In our present study, we found that MDM2 protein level was significantly upregulated in high glucose-treated GMCs, while knocking down MDM2 by siRNA could attenuate high glucose-induced ECM accumulation and GMCs proliferation...
September 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808228/loss-of-usp9x-disrupts-cell-adhesion-and-components-of-the-wnt-and-notch-signaling-pathways-in-neural-progenitors
#17
Susitha Premarathne, Mariyam Murtaza, Nicholas Matigian, Lachlan A Jolly, Stephen A Wood
Development of neural progenitors depends upon the coordination of appropriate intrinsic responses to extrinsic signalling pathways. Here we show the deubiquitylating enzyme, Usp9x regulates components of both intrinsic and extrinsic fate determinants. Nestin-cre mediated ablation of Usp9x from embryonic neural progenitors in vivo resulted in a transient disruption of cell adhesion and apical-basal polarity and, an increased number and ectopic localisation of intermediate neural progenitors. In contrast to other adhesion and polarity proteins, levels of β-catenin protein, especially S33/S37/T41 phospho-β-catenin, were markedly increased in Usp9x (-/Y) embryonic cortices...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28798722/autonomic-neuropathy-and-albuminocytologic-dissociation-in-cerebrospinal-fluid-as-the-presenting-features-of-primary-amyloidosis-a-case-report
#18
Jingjing Li, Yi Li, Hongbing Chen, Shihui Xing, Huiyu Feng, Dawei Liu, Dilong Wang, Jinsheng Zeng, Yuhua Fan
OBJECTIVE: Primary amyloidosis is a disease with a poor prognosis and multi-organ involvement. Here, we report the clinical and pathological features of a patient with primary amyloidosis featuring autonomic neuropathy as the initial symptom and albuminocytologic dissociation in the cerebrospinal fluid (CSF). METHODS: The patient was a 60-year-old Chinese male with numbness, orthostatic hypotension, and gastrointestinal symptoms. For diagnosis, we performed an electromyogram (EMG), lumbar puncture, Bence Jones protein urine test, serum electrophoresis blood test, sural nerve and rectal membrane biopsies, transthyretin (TTR) gene sequencing, and bone marrow puncture...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28771705/selected-signalling-proteins-recruited-to-the-t-cell-receptor-cd3-complex
#19
REVIEW
Jatuporn Ngoenkam, Wolfgang Schamel, Sutatip Pongcharoen
The T cell receptor (TCR)-CD3 complex, expressed on T cells, determines the outcome of a T cell response. It consists of the TCRαβ heterodimer and the non-covalently associated signalling dimers of CD3εγ, CD3εδ and CD3ζζ. TCRαβ binds specifically to a cognate peptide antigen bound to a major histocompatibility complex (MHC) molecule, whereas the CD3 subunits transmit the signal into the cytosol to activate signalling events. Recruitment of proteins to specialized localizations is one mechanism to regulate activation and termination of signalling...
August 3, 2017: Immunology
https://www.readbyqxmd.com/read/28759825/binding-free-energy-calculations-using-mmpb-gbsa-approaches-for-pamam-g4-drug-complexes-at-neutral-basic-and-acid-ph-conditions
#20
Alberto Martínez-Muñoz, Martiniano Bello, Aurelio Romero-Castro, Rolando Alberto Rodríguez-Fonseca, João Rodrigues, Víctor Armando Sánchez-Espinosa, José Correa-Basurto
Dendrimers are synthetic macromolecules with a highly-branched structure and high concentration of surface groups. Among dendrimers, Poly(amidoamine) (PAMAM) has received substantial attention as a novel drug carrier and delivery system. Depending on the generation and type of terminal groups, dendrimer toxicity could change and include cytotoxicity. Although PAMAM is water soluble, molecular modeling of the dendrimer-drug complex is considered challenging for exploring the conformational mobility of dendrimers and atomic specific interactions during the dendrimer-drug association...
July 19, 2017: Journal of Molecular Graphics & Modelling
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