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https://www.readbyqxmd.com/read/28808089/bag3-mediated-proteostasis-at-a-glance
#1
REVIEW
Christina Klimek, Barbara Kathage, Judith Wördehoff, Jörg Höhfeld
Cellular and organismal survival depend on the ability to maintain the proteome, even under conditions that threaten protein integrity. BCL2-associated athanogene 3 (BAG3) is essential for protein homeostasis (proteostasis) in stressed cells. Owing to its multi-domain structure, it engages in diverse processes that are crucial for proteome maintenance. BAG3 promotes the activity of molecular chaperones, sequesters and concentrates misfolded proteins, initiates autophagic disposal, and balances transcription, translation and degradation...
August 14, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28794469/targeting-the-pi3k-akt-mtor-signalling-pathway-in-cystic-fibrosis
#2
R Reilly, M S Mroz, E Dempsey, K Wynne, S J Keely, E F McKone, C Hiebel, C Behl, J A Coppinger
Deletion of phenylalanine 508 of the cystic fibrosis transmembrane conductance regulator (ΔF508 CFTR) is a major cause of cystic fibrosis (CF), one of the most common inherited childhood diseases. ΔF508 CFTR is a trafficking mutant that is retained in the endoplasmic reticulum (ER) and unable to reach the plasma membrane. Efforts to enhance exit of ΔF508 CFTR from the ER and improve its trafficking are of utmost importance for the development of treatment strategies. Using protein interaction profiling and global bioinformatics analysis we revealed mammalian target of rapamycin (mTOR) signalling components to be associated with ∆F508 CFTR...
August 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28755400/mapping-the-in-vitro-interactome-of-cardiac-sodium-na-calcium-ca-2-exchanger-1-ncx1
#3
Tandekile Lubelwana Hafver, Pimthanya Wanichawan, Ornella Manfra, Gustavo Antonio de Souza, Marianne Lunde, Marita Martinsen, William Edward Louch, Ole Mathias Sejersted, Cathrine Rein Carlson
NCX1 is an antiporter membrane protein encoded by the SLC8A1 gene. In the heart, it maintains cytosolic Ca(2+) homeostasis, serving as the primary mechanism for Ca(2+) extrusion during relaxation. Dysregulation of NCX1 is observed in end-stage human heart failure. In this study we used affinity purification coupled with mass spectrometry in rat left ventricle lysates to identify novel NCX1 interacting proteins in the heart. Two screens were conducted using: 1) anti-NCX1 against endogenous NCX1 and 2) anti-His with His-TF-NCX1cyt recombinant protein as bait...
July 28, 2017: Proteomics
https://www.readbyqxmd.com/read/28737514/bag3-plays-a-central-role-in-proteostasis-in-the-heart
#4
Wataru Mizushima, Junichi Sadoshima
Proteinopathies are characterized by the accumulation of misfolded proteins, which ultimately interfere with normal cell function. While neurological diseases, such as Huntington disease and Alzheimer disease, are well-characterized proteinopathies, cardiac diseases have recently been associated with alterations in proteostasis. In this issue of the JCI, Fang and colleagues demonstrate that mice with cardiac-specific deficiency of the co-chaperone protein BCL2-associated athanogene 3 (BAG3) develop dilated cardiomyopathy that is associated with a destabilization of small HSPs as the result of a disrupted interaction between BAG3 and HSP70...
August 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28737513/loss-of-function-mutations-in-co-chaperone-bag3-destabilize-small-hsps-and-cause-cardiomyopathy
#5
Xi Fang, Julius Bogomolovas, Tongbin Wu, Wei Zhang, Canzhao Liu, Jennifer Veevers, Matthew J Stroud, Zhiyuan Zhang, Xiaolong Ma, Yongxin Mu, Dieu-Hung Lao, Nancy D Dalton, Yusu Gu, Celine Wang, Michael Wang, Yan Liang, Stephan Lange, Kunfu Ouyang, Kirk L Peterson, Sylvia M Evans, Ju Chen
Defective protein quality control (PQC) systems are implicated in multiple diseases. Molecular chaperones and co-chaperones play a central role in functioning PQC. Constant mechanical and metabolic stress in cardiomyocytes places great demand on the PQC system. Mutation and downregulation of the co-chaperone protein BCL-2-associated athanogene 3 (BAG3) are associated with cardiac myopathy and heart failure, and a BAG3 E455K mutation leads to dilated cardiomyopathy (DCM). However, the role of BAG3 in the heart and the mechanisms by which the E455K mutation leads to DCM remain obscure...
August 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28724793/a-bag3-chaperone-complex-maintains-cardiomyocyte-function-during-proteotoxic-stress
#6
Luke M Judge, Juan A Perez-Bermejo, Annie Truong, Alexandre Js Ribeiro, Jennie C Yoo, Christina L Jensen, Mohammad A Mandegar, Nathaniel Huebsch, Robyn M Kaake, Po-Lin So, Deepak Srivastava, Beth L Pruitt, Nevan J Krogan, Bruce R Conklin
Molecular chaperones regulate quality control in the human proteome, pathways that have been implicated in many diseases, including heart failure. Mutations in the BAG3 gene, which encodes a co-chaperone protein, have been associated with heart failure due to both inherited and sporadic dilated cardiomyopathy. Familial BAG3 mutations are autosomal dominant and frequently cause truncation of the coding sequence, suggesting a heterozygous loss-of-function mechanism. However, heterozygous knockout of the murine BAG3 gene did not cause a detectable phenotype...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28723972/correction-chaperone-mediated-autophagy-protein-bag3-negatively-regulates-ebola-and-marburg-vp40-mediated-egress
#7
Jingjing Liang, Cari A Sagum, Mark T Bedford, Sachdev S Sidhu, Marius Sudol, Ziying Han, Ronald N Harty
[This corrects the article DOI: 10.1371/journal.ppat.1006132.].
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28703799/bag3-promotes-stem-cell-like-phenotype-in-breast-cancer-by-upregulation-of-cxcr4-via-interaction-with-its-transcript
#8
Bao-Qin Liu, Song Zhang, Si Li, Ming-Xin An, Chao Li, Jing Yan, Jia-Mei Wang, Hua-Qin Wang
BAG3 is an evolutionarily conserved co-chaperone expressed at high levels and has a prosurvival role in many tumor types. The current study reported that BAG3 was induced under specific floating culture conditions that enrich breast cancer stem cell (BCSC)-like cells in spheres. Ectopic BAG3 overexpression increased CD44(+)/CD24(-) CSC subpopulations, first-generation and second-generation mammosphere formation, indicating that BAG3 promotes CSC self-renewal and maintenance in breast cancer. We further demonstrated that mechanically, BAG3 upregulated CXCR4 expression at the post-transcriptional level...
July 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28699904/the-anti-apoptotic-bag3-protein-is-involved-in-braf-inhibitor-resistance-in-melanoma-cells
#9
Luana Guerriero, Giuseppe Palmieri, Margot De Marco, Antonio Cossu, Paolo Remondelli, Mario Capunzo, Maria Caterina Turco, Alessandra Rosati
BAG3 protein, a member of BAG family of co-chaperones, has a pro-survival role in several tumour types. BAG3 anti-apoptotic properties rely on its characteristic to bind several intracellular partners, thereby modulating crucial events such as apoptosis, differentiation, cell motility, and autophagy. In human melanomas, BAG3 positivity is correlated with the aggressiveness of the tumour cells and can sustain IKK-γ levels, allowing a sustained activation of NF-κB. Furthermore, BAG3 is able to modulate BRAFV600E levels and activity in thyroid carcinomas...
June 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28696030/evaluation-of-bag3-levels-in-healthy-subjects-hypertensive-patients-and-hypertensive-diabetic-patients
#10
Giuseppe Derosa, Pamela Maffioli, Alessandra Rosati, Margot De Marco, Anna Basile, Angela D'Angelo, Davide Romano, Amirhossein Sahebkar, Antonia Falco, Maria Caterina Turco
BAG3 is a member of human BAG (Bcl-2-associated athanogene) proteins and plays a role in apoptosis, cell adhesion, cytoskeleton remodeling, and autophagy. The aim of this study was to evaluate BAG3 levels in healthy subjects, hypertensive patients, and hypertensive diabetic patients. We enrolled 209 Caucasian adults, of both sex, 18-75 years of age, 77 were healthy controls, 62 were affected by hypertension, and 70 were affected by hypertension and type 2 diabetes. All patients underwent an assessment that included medical history, physical examination, vital signs, a 12-lead electrocardiogram, measurements of systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), fasting plasma glucose (FPG), glycated hemoglobin (HbA1c ), triglycerides (TG), transaminases, high sensitivity C-reactive protein (Hs-CRP) and BAG3...
July 11, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28685385/exclusive-activation-of-caspase-3-in-mossy-fibers-and-altered-dynamics-of-autophagy-markers-in-the-mice-hippocampus-upon-status-epilepticus-induced-by-kainic-acid
#11
A Rami, A Benz
Epileptic seizures are generally associated with pathological changes in the hippocampus such as astrogliosis, mossy fiber sprouting, and neuronal damage. However, more than 30% of temporal lobe epilepsy in humans shows neither neuronal damage nor mossy fiber sprouting despite chronic epileptic seizures. A similar situation exists in certain commonly used strains of mice, specifically C57BL/6 and BALB/c, which exhibit epileptic seizures, but no neuronal damage upon kainic acid administration. This suggests that intrinsic factors may influence the pathological manifestations of epilepsy...
July 6, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28680391/the-role-of-the-multifunctional-bag3-protein-in-cellular-protein-quality-control-and-in-disease
#12
REVIEW
Elisabeth Stürner, Christian Behl
In neurons, but also in all other cells the complex proteostasis network is monitored and tightly regulated by the cellular protein quality control (PQC) system. Beyond folding of newly synthesized polypeptides and their refolding upon misfolding the PQC also manages the disposal of aberrant proteins either by the ubiquitin-proteasome machinery or by the autophagic-lysosomal system. Aggregated proteins are primarily degraded by a process termed selective macroautophagy (or aggrephagy). One such recently discovered selective macroautophagy pathway is mediated by the multifunctional HSP70 co-chaperone BAG3 (BCL-2-associated athanogene 3)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28680390/the-role-of-the-heat-shock-protein-b8-hspb8-in-motoneuron-diseases
#13
REVIEW
Paola Rusmini, Riccardo Cristofani, Mariarita Galbiati, Maria E Cicardi, Marco Meroni, Veronica Ferrari, Giulia Vezzoli, Barbara Tedesco, Elio Messi, Margherita Piccolella, Serena Carra, Valeria Crippa, Angelo Poletti
Amyotrophic lateral sclerosis (ALS) and spinal and bulbar muscular atrophy (SBMA) are two motoneuron diseases (MNDs) characterized by aberrant protein behavior in affected cells. In familial ALS (fALS) and in SBMA specific gene mutations lead to the production of neurotoxic proteins or peptides prone to misfold, which then accumulate in form of aggregates. Notably, some of these proteins accumulate into aggregates also in sporadic ALS (sALS) even if not mutated. To prevent proteotoxic stresses detrimental to cells, misfolded and/or aggregated proteins must be rapidly removed by the protein quality control (PQC) system...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28669108/novel-genetic-variants-in-bag3-and-tnnt2-in-a-swedish-family-with-a-history-of-dilated-cardiomyopathy-and-sudden-cardiac-death
#14
Eva Fernlund, A Wålinder Österberg, E Kuchinskaya, M Gustafsson, K Jansson, C Gunnarsson
Familial dilated cardiomyopathy is a rare cause of dilated cardiomyopathy (DCM), especially in childhood. Our aim was to describe the clinical course and the genetic variants in a family where the proband was a four-month-old infant presenting with respiratory problems due to DCM. In the family, there was a strong family history of DCM and sudden cardiac death in four generations. DNA was analyzed initially from the deceased girl using next-generation sequencing including 50 genes involved in cardiomyopathy...
August 2017: Pediatric Cardiology
https://www.readbyqxmd.com/read/28628188/silencing-of-bag3-promotes-the-sensitivity-of-ovarian-cancer-cells-to-cisplatin-via-inhibition-of-autophagy
#15
Shuang Qiu, Liang Sun, Ye Jin, Qi An, Changjiang Weng, Jianhua Zheng
Ovarian cancer is the most lethal disease among all gynecological malignancies. Interval cytoreductive surgery and cisplatin‑based chemotherapy are the recommended therapeutic strategies. However, acquired resistance to cisplatin remains a big challenge for the overall survival and prognosis in ovarian cancer. Complicated molecular mechanisms are involved in the process. At present, increasing evidence indicates that autophagy plays an important role in the prosurvival and resistance against chemotherapy...
July 2017: Oncology Reports
https://www.readbyqxmd.com/read/28624440/bag3-promotes-proliferation-of-ovarian-cancer-cells-via-post-transcriptional-regulation-of-skp2-expression
#16
Jing Yan, Chuan Liu, Jing-Yi Jiang, Hans Liu, Chao Li, Xin-Yu Li, Ye Yuan, Zhi-Hong Zong, Hua-Qin Wang
Bcl-2 associated athanogene 3 (BAG3) contains a modular structure, through which BAG3 interacts with a wide range of proteins, thereby affording its capacity to regulate multifaceted biological processes. BAG3 is often highly expressed and functions as a pro-survival factor in many cancers. However, the oncogenic potential of BAG3 remains not fully understood. The cell cycle regulator, S-phase kinase associated protein 2 (Skp2) is increased in various cancers and plays an important role in tumorigenesis. The current study demonstrated that BAG3 promoted proliferation of ovarian cancer cells via upregulation of Skp2...
June 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28599417/overexpression-of-the-anti-apoptotic-protein-bag3-in-human-choroidal-melanoma-a-case-report
#17
Tatsuya Yunoki, Yoshiaki Tabuchi, Takashi Kondo, Yoko Ishii, Atsushi Hayashi
Bcl-2-associated athanogene 3 (BAG3), a co-chaperone of heat shock protein 70 (HSP70), exerts anti-apoptotic effects in various malignant tumors. However, relationships between choroidal melanoma and BAG3 are poorly studied. This study investigated the expression of BAG3 in a case of human choroidal melanoma. Funduscopy, computed tomography, and single-photon emission computed tomography with the intravenous injection of N-isopropyl-p-[(123)I] iodoamphetamine strongly indicated choroidal melanoma in a 68-year-old woman...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28442482/bag3-bcl-2-associated-athanogene-3-coding-variant-in-mice-determines-susceptibility-to-ischemic-limb-muscle-myopathy-by-directing-autophagy
#18
Joseph M McClung, Timothy J McCord, Terence E Ryan, Cameron A Schmidt, Tom D Green, Kevin W Southerland, Jessica L Reinardy, Sarah B Mueller, Talaignair N Venkatraman, Christopher D Lascola, Sehoon Keum, Douglas A Marchuk, Espen E Spangenburg, Ayotunde Dokun, Brian H Annex, Christopher D Kontos
BACKGROUND: Critical limb ischemia is a manifestation of peripheral artery disease that carries significant mortality and morbidity risk in humans, although its genetic determinants remain largely unknown. We previously discovered 2 overlapping quantitative trait loci in mice, Lsq-1 and Civq-1, that affected limb muscle survival and stroke volume after femoral artery or middle cerebral artery ligation, respectively. Here, we report that a Bag3 variant (Ile81Met) segregates with tissue protection from hind-limb ischemia...
July 18, 2017: Circulation
https://www.readbyqxmd.com/read/28436997/truncating-mutations-on-myofibrillar-myopathies-causing-genes-as-prevalent-molecular-explanations-on-patients-with-dilated-cardiomyopathy
#19
Alexandre Janin, Karine N'Guyen, Gilbert Habib, Claire Dauphin, Valérie Chanavat, Patrice Bouvagnet, Romain Eschalier, Streichenberger Nathalie, Philippe Chevalier, Gilles Millat
Dilated Cardiomyopathy (DCM) is one of the leading causes of heart failure with high morbidity and mortality. More than 40 genes have been reported to cause DCM. To provide new insights into the pathophysiology of dilated cardiomyopathy, a NGS workflow based on a panel of 48 cardiomyopathies-causing genes was used to analyze a cohort of 222 DCM patients. Truncating variants were detected on 63 unrelated DCM cases (28.4%). Most of them were identified, as expected, on TTN (29 DCM probands), but truncating variants were also identified on myofibrillar myopathies causing genes in 17 DCM patients (7...
April 24, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/28402699/inhibition-of-retrograde-transport-modulates-misfolded-protein-accumulation-and-clearance-in-motoneuron-diseases
#20
Riccardo Cristofani, Valeria Crippa, Paola Rusmini, Maria Elena Cicardi, Marco Meroni, Nausicaa V Licata, Gessica Sala, Elisa Giorgetti, Christopher Grunseich, Mariarita Galbiati, Margherita Piccolella, Elio Messi, Carlo Ferrarese, Serena Carra, Angelo Poletti
Motoneuron diseases, like spinal bulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis (ALS), are associated with proteins that because of gene mutation or peculiar structures, acquire aberrant (misfolded) conformations toxic to cells. To prevent misfolded protein toxicity, cells activate a protein quality control (PQC) system composed of chaperones and degradative pathways (proteasome and autophagy). Inefficient activation of the PQC system results in misfolded protein accumulation that ultimately leads to neuronal cell death, while efficient macroautophagy/autophagy-mediated degradation of aggregating proteins is beneficial...
April 12, 2017: Autophagy
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