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APPL1

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https://www.readbyqxmd.com/read/29021281/survival-of-brca2-deficient-cells-is-promoted-by-gipc3-a-novel-genetic-interactor-of%C3%A2-brca2
#1
Xia Ding, Subha Philip, Betty K Martin, Yan Pang, Sandra Burkett, Deborah A Swing, Chinmayi Pamala, Daniel A Ritt, Ming Zhou, Deborah K Morrison, Xinhua Ji, Shyam K Sharan
BRCA2 loss-of-heterozygosity (LOH) is frequently observed in BRCA2-mutated tumors, but its bi-allelic loss causes embryonic lethality in mice and inhibits proliferation of normal somatic cells. Therefore, it remains unclear how loss of BRCA2 contributes to tumorigenesis. One possibility is that mutation in potential genetic interactors of BRCA2, such as TRP53, is required for cell survival/proliferation in the absence of BRCA2. In this study, using an insertional mutagenesis screen in mouse embryonic stem cells (mESC), we have identified GIPC3 (GAIP-interacting protein C-terminus 3) as a BRCA2 genetic interactor that contributes to survival of Brca2-null mESC...
October 11, 2017: Genetics
https://www.readbyqxmd.com/read/28946816/effect-of-tnf-%C3%AE-on-molecules-related-to-the-insulin-action-in-endometrial-cells-exposed-to-hyperandrogenic-and-hyperinsulinic-conditions-characteristics-of-polycystic-ovary-syndrome
#2
Lorena Oróstica, Paula García, Carolina Vera, Víctor García, Carmen Romero, Margarita Vega
Polycystic ovary syndrome (PCOS) affects not only ovarian functions but is also able to affect endometrium metabolism. Around 80% of women with PCOS are obese. High tumor necrosis factor (TNF)-α production and low adiponectin levels are characteristics of obesity. Interestingly, endometrium from obese women with PCOS presents an insulin-resistance condition, high TNF-α levels, and low adiponectin levels. However, TNF-α effect on molecules associated with insulin action in endometrial cells remains unclear...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28902365/appl1-promotes-the-migration-of-gastric-cancer-cells-by-regulating-akt2-phosphorylation
#3
Yingxun Liu, Chunli Zhang, Lingyu Zhao, Ning Du, Ni Hou, Tusheng Song, Chen Huang
As a multifunctional adaptor protein, APPL1 (adaptor protein containing pleckstrin homology domain, phosphotyrosine binding domain and a leucine zipper motif 1) is overexpressed in many cancers, and has been implicated in tumorigenesis and tumor progression. The present study investigated the expression of APPL1 in gastric carcinoma and the function in regulating cell migration. We investigated the expression of APPL1 in gastric carcinoma based upon The Cancer Genome Atlas (TCGA) database. The expression of APPL1 in collected gastric carcinoma tissues and cultured cells was measured by qRT-PCR and western blot analysis...
September 5, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28620038/appl1-is-a-multifunctional-endosomal-signaling-adaptor-protein
#4
REVIEW
Nicole L Diggins, Donna J Webb
Endosomal adaptor proteins are important regulators of signaling pathways underlying many biological processes. These adaptors can integrate signals from multiple pathways via localization to specific endosomal compartments, as well as through multiple protein-protein interactions. One such adaptor protein that has been implicated in regulating signaling pathways is the adaptor protein containing a pleckstrin homology (PH) domain, phosphotyrosine-binding (PTB) domain, and leucine zipper motif 1 (APPL1). APPL1 localizes to a subset of Rab5-positive endosomes through its Bin-Amphiphysin-Rvs and PH domains, and it coordinates signaling pathways through its interaction with many signaling receptors and proteins through its PTB domain...
June 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28593738/sex-differences-in-the-regulation-of-porcine-coronary-artery-tone-by-perivascular-adipose-tissue-a-role-of-adiponectin
#5
Abdulla A Ahmad, Michael D Randall, Richard E Roberts
BACKGROUND AND PURPOSE: As there is sexual dimorphism in the regulation of vascular tone, the aim of this present study was to determine whether there are sex differences in perivascular adipose tissue (PVAT)-mediated regulation of the porcine coronary artery (PCA) tone. EXPERIMENTAL APPROACH: Isometric tension recording system was used to record changes in tone in PCAs. Western blot analysis was performed to examine the expression of adiponectin in PVAT and adiponectin receptors and adiponectin binding protein (APPL1) in PCA...
August 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28591580/myo6-regulates-spatial-organization-of-signaling-endosomes-driving-akt-activation-and-actin-dynamics
#6
Thomas A Masters, David A Tumbarello, Margarita V Chibalina, Folma Buss
APPL1- and RAB5-positive signaling endosomes play a crucial role in the activation of AKT in response to extracellular stimuli. Myosin VI (MYO6) and two of its cargo adaptor proteins, GIPC and TOM1/TOM1L2, localize to these peripheral endosomes and mediate endosome association with cortical actin filaments. Loss of MYO6 leads to the displacement of these endosomes from the cell cortex and accumulation in the perinuclear space. Depletion of this myosin not only affects endosome positioning, but also induces actin and lipid remodeling consistent with endosome maturation, including accumulation of F-actin and the endosomal lipid PI(3)P...
June 6, 2017: Cell Reports
https://www.readbyqxmd.com/read/28585210/adiponectin-resistance-in-obesity
#7
REVIEW
Atilla Engin
The decrease in adiponectin levels are negatively correlated with chronic subclinical inflammation markers in obesity. The hypertrophic adipocytes cause obesity-linked insulin resistance and metabolic syndrome. Furthermore, macrophage polarization is a key determinant regulating adiponectin receptor (AdipoR1/R2) expression and differential adiponectin-mediated macrophage inflammatory responses in obese individuals. In addition to decrease in adiponectin concentrations, the decline in AdipoR1/R2 mRNA expression leads to a decrement in adiponectin binding to cell membrane, and this turns into attenuation in the adiponectin effects...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28472298/adiponectin-stimulates-lipid-metabolism-via-ampk-in-rabbit-blastocysts
#8
Maria Schindler, Mareike Pendzialek, Katarzyna Joanna Grybel, Tom Seeling, Jacqueline Gürke, Bernd Fischer, Anne Navarrete Santos
STUDY QUESTION: How does a maternal diabetic hyperadiponectineamia affect signal transduction and lipid metabolism in rabbit preimplantation blastocysts? SUMMARY ANSWER: In a diabetic pregnancy increased levels of adiponectin led to a switch in embryonic metabolism towards a fatty acid-dependent energy metabolism, mainly affecting genes that are responsible for fatty acid uptake and turnover. WHAT IS KNOWN ALREADY: Although studies in cell culture experiments have shown that adiponectin is able to regulate lipid metabolism via 5'-AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor α (PPARα), data on the effects of adiponectin on embryonic lipid metabolism are not available...
July 1, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28415720/the-function-of-oxytocin-a-potential-biomarker-for-prostate-cancer-diagnosis-and-promoter-of-prostate-cancer
#9
Huan Xu, Shi Fu, Qi Chen, Meng Gu, Juan Zhou, Chong Liu, Yanbo Chen, Zhong Wang
PURPOSE: To measure the level of oxytocin in serum and prostate cancer (PCa) tissue and study its effect on the proliferation of PCa cells. RESULTS: Oxytocin level in serum was significantly increased in PCa patients compared with the no-carcinoma individuals. Additionally, the levels of oxytocin and its receptor were also elevated in the PCa tissue. However, no significant difference existed among the PCa of various Gleason grades. Western blot analysis confirmed the previous results and revealed an increased expression level of APPL1...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28176455/adiponectin-promotes-human-jaw-bone-marrow-mesenchymal-stem-cell-chemotaxis-via-cxcl1-and-cxcl8
#10
Yinfei Pu, Mengke Wang, Yingying Hong, Yuwei Wu, Zhihui Tang
Adiponectin (APN) is known to promote the osteogenic differentiation of human jaw bone marrow mesenchymal stem cells (h-JBMMSCs). However, the underlying mechanism has not been fully elucidated. Previously, we showed that APN could promote h-JBMMSC osteogenesis via APPL1-p38 by up-regulating osteogenesis-related genes. Here, we aimed to determine whether APN could promote h-JBMMSC chemotaxis through CXCL1/CXCL8. The CCK-8, wound healing and transwell assays were used to evaluate the proliferation, migration and chemotaxis of h-JBMMSCs with or without APN treatment...
July 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28143933/filopodia-formation-and-endosome-clustering-induced-by-mutant-plus-end-directed-myosin-vi
#11
Thomas A Masters, Folma Buss
Myosin VI (MYO6) is the only myosin known to move toward the minus end of actin filaments. It has roles in numerous cellular processes, including maintenance of stereocilia structure, endocytosis, and autophagosome maturation. However, the functional necessity of minus-end-directed movement along actin is unclear as the underlying architecture of the local actin network is often unknown. To address this question, we engineered a mutant of MYO6, MYO6+, which undergoes plus-end-directed movement while retaining physiological cargo interactions in the tail...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28108259/appls-more-than-just-adiponectin-receptor-binding-proteins
#12
REVIEW
Zhuoying Liu, Ting Xiao, Xiaoyu Peng, Guangdi Li, Fang Hu
APPLs (adaptor proteins containing the pleckstrin homology domain, phosphotyrosine binding domain and leucine zipper motif) are multifunctional adaptor proteins that bind to various membrane receptors, nuclear factors and signaling proteins to regulate many biological activities and processes, such as cell proliferation, chromatin remodeling, endosomal trafficking, cell survival, cell metabolism and apoptosis. APPL1, one of the APPL isoforms, was the first identified protein and interacts directly with adiponectin receptors to mediate adiponectin signaling to enhance lipid oxidation and glucose uptake...
January 17, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28011992/appl1-prevents-pancreatic-beta-cell-death-and-inflammation-by-dampening-nf%C3%AE%C2%BAb-activation-in-a-mouse-model-of-type-1-diabetes
#13
Xue Jiang, Yawen Zhou, Kelvin K L Wu, Zhanrui Chen, Aimin Xu, Kenneth K Y Cheng
AIMS/HYPOTHESIS: Beta cell inflammation and demise is a feature of type 1 diabetes. The insulin-sensitising molecule 'adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1' (APPL1), which contains an NH2-terminal Bin/Amphiphysin/Rvs domain, a central pleckstrin homology domain and a COOH-terminal phosphotyrosine-binding domain, has been shown to modulate inflammatory response in various cell types but its role in regulating beta cell mass and inflammation in type 1 diabetes remains unknown...
March 2017: Diabetologia
https://www.readbyqxmd.com/read/27916608/functional-properties-of-hepatocytes-in-vitro-are-correlated-with-cell-polarity-maintenance
#14
Anja Zeigerer, Anne Wuttke, Giovanni Marsico, Sarah Seifert, Yannis Kalaidzidis, Marino Zerial
Exploring the cell biology of hepatocytes in vitro could be a powerful strategy to dissect the molecular mechanisms underlying the structure and function of the liver in vivo. However, this approach relies on appropriate in vitro cell culture systems that can recapitulate the cell biological and metabolic features of the hepatocytes in the liver whilst being accessible to experimental manipulations. Here, we adapted protocols for high-resolution fluorescence microscopy and quantitative image analysis to compare two primary hepatocyte culture systems, monolayer and collagen sandwich, with respect to the distribution of two distinct populations of early endosomes (APPL1 and EEA1-positive), endocytic capacity, metabolic and signaling activities...
January 1, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/27820851/appl1-mediating-leptin-signaling-contributes-to-proliferation-and-migration-of-cancer-cells
#15
Youming Ding, Yingkang Cao, Bin Wang, Lei Wang, Yemin Zhang, Deling Zhang, Xiaoyan Chen, Mingxin Li, Changhua Wang
Leptin has been implicated in tumorigenesis and tumor progression, particularly in obese patients. As a multifunctional adaptor protein, APPL1 (containing pleckstrin homology domain, phosphotyrosine binding domain, and a leucine zipper motif 1) plays a critical role in regulating adiponectin and insulin signaling pathways. Currently, high APPL1 level has been suggested to be related to metastases and progression of some types of cancer. However, the intercourse between leptin signaling pathway and APPL1 remains poorly understood...
2016: PloS One
https://www.readbyqxmd.com/read/27771154/incretin-treatment-and-atherosclerotic-plaque-stability-role-of-adiponectin-appl1-signaling-pathway
#16
Michelangela Barbieri, Raffaele Marfella, Antonietta Esposito, Maria Rosaria Rizzo, Edith Angellotti, Ciro Mauro, Mario Siniscalchi, Fabio Chirico, Pasquale Caiazzo, Fulvio Furbatto, Alessandro Bellis, Nunzia D'Onofrio, Milena Vitiello, Franca Ferraraccio, Giuseppe Paolisso, Maria Luisa Balestrieri
AIMS: Glucagon like peptide 1 (GLP-1) analogues and dipeptidyl peptidase IV (DPP-4) inhibitors reduce atherosclerosis progression in type 2 diabetes mellitus (T2DM) patients and are associated with morphological and compositional characteristics of stable plaque phenotype. GLP-1 promotes the secretion of adiponectin which exerts anti-inflammatory effects through the adaptor protein PH domain and leucine zipper containing 1 (APPL1). The potential role of APPL1 expression in the evolution of atherosclerotic plaque in TDM2 patients has not previously evaluated...
October 5, 2016: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/27763641/pkn2-and-cdo-interact-to-activate-akt-and-promote-myoblast-differentiation
#17
Sang-Jin Lee, Jeongmi Hwang, Hyeon-Ju Jeong, Miran Yoo, Ga-Yeon Go, Jae-Rin Lee, Young-Eun Leem, Jong Woo Park, Dong-Wan Seo, Yong Kee Kim, Myong-Joon Hahn, Jeung-Whan Han, Jong-Sun Kang, Gyu-Un Bae
Skeletal myogenesis is coordinated by multiple signaling pathways that control cell adhesion/migration, survival and differentiation accompanied by muscle-specific gene expression. A cell surface protein Cdo is involved in cell contact-mediated promyogenic signals through activation of p38MAPK and AKT. Protein kinase C-related kinase 2 (PKN2/PRK2) is implicated in regulation of various biological processes, including cell migration, adhesion and death. It has been shown to interact with and inhibit AKT thereby inducing cell death...
October 20, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27659231/erratum-appl1-counteracts-obesity-induced-vascular-insulin-resistance-and-endothelial-dysfunction-by-modulating-the-endothelial-production-of-nitric-oxide-and-endothelin-1-in-mice-diabetes-2011-60-3044-3054
#18
Yi Wang, Kenneth K Y Cheng, Karen S L Lam, Donghai Wu, Yu Wang, Yu Huang, Paul M Vanhoutte, Gary Sweeney, Yiming Li, Aimin Xu
No abstract text is available yet for this article.
October 2016: Diabetes
https://www.readbyqxmd.com/read/27659229/erratum-adiponectin-induced-endothelial-nitric-oxide-synthase-activation-and-nitric-oxide-production-are-mediated-by-appl1-in-endothelial-cells-diabetes-2007-56-1387-1394
#19
Kenneth K Y Cheng, Karen S L Lam, Yu Wang, Yu Huang, David Carling, Donghai Wu, Chiwai Wong, Aimin Xu
No abstract text is available yet for this article.
October 2016: Diabetes
https://www.readbyqxmd.com/read/27632382/effects-of-training-and-detraining-on-adiponectin-plasma-concentration-and-muscle-sensitivity-in-lean-and-overweight-men
#20
Caroline Gastebois, Clément Villars, Jocelyne Drai, Emmanuelle Canet-Soulas, Stéphane Blanc, Audrey Bergouignan, Etienne Lefai, Chantal Simon
PURPOSE: To delineate the direct effect of physical activity on adiponectin metabolism, we investigated the impact of contrasted physical activity changes, independent of body mass changes, on adiponectin plasma concentration and muscle sensitivity in lean and overweight adult males. METHODS: Eleven physically active lean men (70.6 ± 2.1 kg) were subjected to 1-month detraining; 9 sedentary lean men (73.1 ± 3.3 kg); and 11 sedentary overweight men (97.5 ± 3...
December 2016: European Journal of Applied Physiology
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