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Numb protein

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https://www.readbyqxmd.com/read/29042443/mammalian-numb-protein-antagonizes-notch-by-controlling-postendocytic-trafficking-of-the-notch-ligand-delta-like-4
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
https://www.readbyqxmd.com/read/28751447/numb-low-enriches-a-castration-resistant-prostate-cancer-cell-subpopulation-associated-with-enhanced-notch-and-hedgehog-signaling
#8
Yanjing Guo, Kai Zhang, Chaping Cheng, Zhongzhong Ji, Xue Wang, Minglei Wang, Mingliang Chu, Dean G Tang, Helen He Zhu, Wei-Qiang Gao
Purpose: To elucidate the role and molecular mechanism of Numb in prostate cancer and the functional contribution of Numb(-/low) prostate cancer cells in castration resistance.Experimental Design: The expression of Numb was assessed using multiple Oncomine datasets and prostate cancer tissues from both humans and mice. The biological effects of the overexpression and knockdown of Numb in human prostate cancer cell lines were investigated in vitro and in vivo In addition, we developed a reliable approach to distinguish between prostate cancer cell populations with a high or low endogenous expression of Numb protein using a Numb promoter-based lentiviral reporter system...
July 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28720501/numb-positively-regulates-autophagic-flux-via-regulating-lysosomal-function
#9
Haiyan Sun, Yi Liu, Lei Zhang, Ximing Shao, Ke Liu, Zhihao Ding, Xianming Liu, Changan Jiang, Huashun Li, Hongchang Li
Autophagy is a lysosome-dependent catabolic process involving in the degradation and recycling of unnecessary or damaged proteins and organelles. Emerging evidence indicates that autophagy dysfunction is closely related to various human diseases including cancer, aging, myopathies and neurodegenerative disorders. Here, using genetic knockdown, we uncover the role of Numb, an endocytic adaptor protein, in regulating the late steps of autophagy. We found that Numb depletion led to the accumulation of autophagic vacuole, as verified by RFP-LC3 staining combined with transmission electron microscopy...
September 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28705754/progression-of-lyme-disease-to-bell-s-palsy-despite-treatment-with-doxycycline
#10
Luis A Marcos, Zengmin Yan
No abstract text is available yet for this article.
September 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28680318/clinical-electrophysiological-and-serological-evaluation-of-patients-with-cramp-fasciculation-syndrome
#11
Mürüvvet Poyraz, Zeliha Matur, Fikret Aysal, Erdem Tüzün, Lütfü Hanoğlu, A Emre Öge
INTRODUCTION: Cramp-fasciculation syndrome (CFS) is a rare peripheral nerve hyperexcitability syndrome. There are only a few reports on clinical and serological profile of a CFS cohort that was followed up by a single outpatient clinic. METHODS: Clinical, electrophysiological, and serological features of 6 CFS patients (5 men, 1 woman; 27-65 years old) were investigated. RESULTS: All patients presented with cramps, fasciculations, muscle pain, and autonomic symptoms, and 2 also reported numbness and burning sensation in limbs, suggestive of neuropathic pain...
June 2017: Noro Psikiyatri Arsivi
https://www.readbyqxmd.com/read/28644254/sporadic-creutzfeldt-jakob-disease-with-unilateral-symptoms-in-the-setting-of-metastatic-renal-cell-carcinoma
#12
Kyle C Rossi, Christine M Stahl, Pengfei Zhang, John W Liang, Lara V Marcuse, Fred Lublin
INTRODUCTION: Although it is not rare for magnetic resonance imaging findings in Creutzfeldt-Jakob disease to be asymmetric, unilateral clinical syndromes are uncommonly reported and may confound diagnosis. In addition, neurological paraneoplastic syndromes are not common in renal cell carcinoma, though there are cases reported, often without an offending antibody isolated. CASE REPORT: A 66-year-old man was admitted with 1 month of left-sided numbness and "loss of control" of the left arm...
July 2017: Neurologist
https://www.readbyqxmd.com/read/28641615/-expression-and-asymmetric-division-of-numb-in-leukemia-cell-k562-line
#13
Zheng Li, Huan Li, Yi-Hui Li, Ying-Xi Xu, Hai-Yan Xing, Ke-Jing Tang, Zheng Tian, Min Wang, Qing Rao
OBJECTIVE: To investigate the role of asymmetric division in leukemia cells through detection of expression and asymmetric division of Numb in differentiated and undifferentiated K562 cells. METHODS: Firstly, Hemin was used to induce K562 cell differentiation, and the expression of Numb was detected by the real-time quantitative RT-PCR and flow cytometry. After K562 cells were synchronized by nocodazole, the Numb protein was labeled by immunohistochemical staining, followed by the determination of the terminally differentiated cells through confocal microscopy...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28612563/-expression-and-clinical-significance-of-numb-and-p53-proteins-in-epithelial-ovarian-carcinoma
#14
Min Xu, Hong-Ju He, Huan Zhang, Ao Wang, Jie Chen
OBJECTIVES: To investigate the expression and clinical significance of Numb and P53 proteins in epithelial ovarian carcinoma. METHODS: We co-tested the expressions of Numb and P53 proteins in epithelial ovarian tissues by immunohistochemistry, including 20 cases of normal tissues, 29 cases of benign tumors, 35 cases of borderline ovarian tumors and 87 cases of epithelial ovarian carcinoma. Their clinical significance was analyzed. RESULTS: The positive expression rates of Numb protein in normal ovarian tissues, benign ovarian tumors, borderline ovarian tumors and epithelial ovarian carcinoma were 5%, 13...
January 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28598117/-expression-level-of-membrane-associated-proteins-numb-in-epithelial-ovarian-carcinoma-and-its-relationship
#15
Hong Jing, Xiao-Yu Liu, Ya-Li Chen, Li-Ping Bai, Ai Zheng
OBJECTIVES: To explore the expression level of membrane-associated protein Numb in epithelial ovarian carcinoma and its relationship with ovarian cancer stem cell markers CD117,CD133,acetaldehyde dehydrogenase 1(ALDH1). METHODS: A total of 136 patients who had ovarian tumors and 22 patients who had not ovarian tumors in Department of Gynaecology and Obstetrics,West China Second University Hospital,Sichuan University were chosen as the study subjects.According to the histopathologic examination results,they were divided into epithelial ovarian carcinoma group (n=92),ovarian borderline tumor group (n=23),ovarian benign tumor group (n=21) and normal ovary group (n=22)...
November 2016: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28587194/cross-kingdom-regulation-of-putative-mirnas-derived-from-happy-tree-in-cancer-pathway-a-systems-biology-approach
#16
Dinesh Kumar, Swapnil Kumar, Garima Ayachit, Shivarudrappa B Bhairappanavar, Afzal Ansari, Priyanka Sharma, Subhash Soni, Jayashankar Das
MicroRNAs (miRNAs) are well-known key regulators of gene expression primarily at the post-transcriptional level. Plant-derived miRNAs may pass through the gastrointestinal tract, entering into the body fluid and regulate the expression of endogenous mRNAs. Camptotheca acuminata, a highly important medicinal plant known for its anti-cancer potential was selected to investigate cross-kingdom regulatory mechanism and involvement of miRNAs derived from this plant in cancer-associated pathways through in silico systems biology approach...
June 3, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28577495/knockdown-of-long-noncoding-rna-ghet1-inhibits-cell-activation-of-gastric-cancer
#17
Hui Huang, Wenjun Liao, Xueqiang Zhu, Hao Liu, Lijun Cai
OBJECTION: The aim of this study was to evaluate the effects of lncRNA GHET1 in developing of Gastric Cancer. METHODS: Collecting the 20 gastric cancer patients and evaluated the pathological of adjacent and tumor tissues by HE stating. We analyzed the protein expression of Numb in gastric cancer (GC) tissues by using IHC and the gene expression of Numb and GHET1 in adjacent and GC tissues by RT-PCR. The AGS cells were divided into 3 groups: Control (Co), NC and shRNA groups...
August 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28531799/numb-had-anti-tumor-effects-in-prostatic-cancer
#18
Ji Sun, Kai Wang, Jingfei Teng, Yufu Yu, Runmiao Hua, Haiyong Zhou, Dachuan Zhong, Yi Fan
AIM: The aim of this study was to explain the Numb anti-cancer effects in the prostatic cancer. METHODS: Collecting the 20 prostatic cancer patients and analyzing the correlation between Numb and Glease score. Transfection Numb into DU-145 and PC-3 cells, measuring the proliferation rate of difference groups by MTT assay, evaluating the cell apoptosis and cell cycle of difference group by Flow cytometry; measuring the invasion and migration abilities by transwell and wound healing assays...
August 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28503308/portal-hypertension-as-the-initial-manifestation-of-poems-syndrome-a-case-report
#19
Lina Wu, Yue Li, Fang Yao, Chongmei Lu, Jian Li, Weixun Zhou, Jiaming Qian
BACKGROUND: Portal hypertension has a broad differential diagnosis. POEMS syndrome is an uncommon cause of it. POEMS syndrome is a rare disease involving multiple organs. In differential diagnosis of portal hypertension, POEMS syndrome should be considered especially when other symptoms such as numbness, organomegaly, endocrine alteration and skin changes also present, as it is highlighted by our case. CASE PRESENTATION: We report a 46-year-old Chinese male, a teacher, presenting with portal hypertension...
2017: BMC Hematology
https://www.readbyqxmd.com/read/28439677/ap-2%C3%AE-reverses-vincristine-induced-multidrug-resistance-of-sgc7901-gastric-cancer-cells-by-inhibiting-the-notch-pathway
#20
Wei Lian, Li Zhang, Long Yang, Wensheng Chen
Multidrug resistance (MDR) remains a major clinical obstacle in the treatment of gastric cancer (GC) since it causes tumor recurrence and metastasis. The transcription factor activator protein-2α (AP-2α) has been implicated in drug-resistance in breast cancer; however, its effects on MDR of gastric cancer are far from understood. In this study, we aimed to explore the effects of AP-2α on the MDR in gastric cancer cells selected by vincristine (VCR). Decreased AP-2α levels were markedly detected by RT-PCR and Western blot in gastric cancer cell lines (BGC-823, SGC-7901, AGS, MKN-45) compared with that in the gastric epithelial cell line (GES-1)...
July 2017: Apoptosis: An International Journal on Programmed Cell Death
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