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https://www.readbyqxmd.com/read/29114069/bag3-directly-stabilizes-hexokinase-2-mrna-and-promotes-aerobic-glycolysis-in-pancreatic-cancer-cells
#1
Ming-Xin An, Si Li, Han-Bing Yao, Chao Li, Jia-Mei Wang, Jia Sun, Xin-Yu Li, Xiao-Na Meng, Hua-Qin Wang
Aerobic glycolysis, a phenomenon known historically as the Warburg effect, is one of the hallmarks of cancer cells. In this study, we characterized the role of BAG3 in aerobic glycolysis of pancreatic ductal adenocarcinoma (PDAC) and its molecular mechanisms. Our data show that aberrant expression of BAG3 significantly contributes to the reprogramming of glucose metabolism in PDAC cells. Mechanistically, BAG3 increased Hexokinase 2 (HK2) expression, the first key enzyme involved in glycolysis, at the posttranscriptional level...
November 7, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29113311/the-anti-apoptotic-bag3-protein-is-involved-in-braf-inhibitor-resistance-in-melanoma-cells
#2
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...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29068469/bag3-dependent-expression-of-mcl-1-confers-resistance-of-mutant-kras-colon-cancer-cells-to-the-hsp90-inhibitor-auy922
#3
Chun Yan Wang, Su Tang Guo, Amanda Croft, Xu Guang Yan, Lei Jin, Xu Dong Zhang, Chen Chen Jiang
Past studies have shown that mutant KRAS colon cancer cells are susceptible to apoptosis induced by the HSP90 inhibitor AUY922. Nevertheless, intrinsic and acquired resistance remains an obstacle for the potential application of the inhibitor in the treatment of the disease. Here we report that Mcl-1 is important for survival of colon cancer cells in the presence of AUY922. Mcl-1 was upregulated in mutant KRAS colon cancer cells selected for resistance to AUY922-induced apoptosis. This was due to its increased stability mediated by Bcl-2-associated athanogene domain 3 (BAG3), which was also increased in resistant colon cancer cells by heat shock factor 1 (HSF1) as a result of chronic endoplasmic reticulum (ER) stress...
October 25, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28978976/subcutaneous-adipose-tissue-gene-expression-and-dna-methylation-respond-to-both-short-and-long-term-weight-loss
#4
S Bollepalli, S Kaye, S Heinonen, J Kaprio, A Rissanen, K A Virtanen, K H Pietiläinen, M Ollikainen
BACKGROUND: Few studies have examined both gene expression and DNA methylation profiles in subcutaneous adipose tissue (SAT) during long-term weight loss. Thus molecular mechanisms in weight loss and regain remain elusive. PARTICIPANTS/METHODS: We performed a one-year weight loss intervention on 19 healthy obese participants (mean BMI 34.6 kg/m(2)) and studied longitudinal gene expression (Affymetrix Human Genome U133 Plus 2.0) and DNA methylation (Infinium HumanMethylation450 BeadChip) in SAT at 0, 5 and 12 months...
October 5, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28941726/a-role-of-bag3-in-regulating-snca-%C3%AE-synuclein-clearance-via-selective-macroautophagy
#5
Yu-Lan Cao, Ya-Ping Yang, Cheng-Jie Mao, Xiao-Qi Zhang, Chen-Tao Wang, Jing Yang, Dong-Jun Lv, Fen Wang, Li-Fang Hu, Chun-Feng Liu
Many studies reveal that BAG3 plays a critical role in the regulation of protein degradation via macroautophagy. However, it remains unknown whether BAG3 affects the quality control of α-synuclein (SNCA), a Parkinson's disease-related protein. In this study, we demonstrated the increases of BAG3 expression in the ventral midbrain of SNCA(A53T) transgenic mice and also in MG132-treated PC12 cells overexpressing wild-type SNCA (SNCA(WT)-PC12). Moreover, we showed that BAG3 overexpression was sufficient to enhance the autophagy activity while knockdown of Bag3 reduced it in SNCA(WT)-PC12 cells...
December 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28933591/suppression-of-chrn-endocytosis-by-carbonic-anhydrase-car3-in-the-pathogenesis-of-myasthenia-gravis
#6
Ailian Du, Shiqian Huang, Xiaonan Zhao, Kuan Feng, Shuangyan Zhang, Jiefang Huang, Xiang Miao, Fulvio Baggi, Rennolds S Ostrom, Yanyun Zhang, Xiangjun Chen, Congfeng Xu
Myasthenia gravis is an autoimmune disorder of the neuromuscular junction manifested as fatigable muscle weakness, which is typically caused by pathogenic autoantibodies against postsynaptic CHRN/AChR (cholinergic receptor nicotinic) in the endplate of skeletal muscle. Our previous studies have identified CA3 (carbonic anhydrase 3) as a specific protein insufficient in skeletal muscle from myasthenia gravis patients. In this study, we investigated the underlying mechanism of how CA3 insufficiency might contribute to myasthenia gravis...
September 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28905214/mir-217-5p-induces-apoptosis-by-directly-targeting-prkci-bag3-itgav-and-mapk1-in-colorectal-cancer-cells
#7
Marion Flum, Michael Kleemann, Helga Schneider, Benjamin Weis, Simon Fischer, René Handrick, Kerstin Otte
Apoptosis is a genetically directed process of programmed cell death. A variety of microRNAs (miRNAs), endogenous single-stranded non-coding RNAs of about 22 nucleotides in length have been shown to be involved in the regulation of the intrinsic or extrinsic apoptotic pathways. There is increasing evidence that the aberrant expression of miRNAs plays a causal role in the development of diseases such as cancer. This makes miRNAs promising candidate molecules as therapeutic targets or agents. MicroRNA (miR)-217-5p has been implicated in carcinogenesis of various cancer entities, including colorectal cancer...
September 14, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28864347/role-of-bag3-in-cancer-progression-a-therapeutic-opportunity
#8
REVIEW
Margot De Marco, Anna Basile, Vittoria Iorio, Michelina Festa, Antonia Falco, Bianca Ranieri, Maria Pascale, Gianluca Sala, Paolo Remondelli, Mario Capunzo, Matthew A Firpo, Raffaele Pezzilli, Liberato Marzullo, Pierpaolo Cavallo, Vincenzo De Laurenzi, Maria Caterina Turco, Alessandra Rosati
BAG3 is a multifunctional protein that can bind to heat shock proteins (Hsp) 70 through its BAG domain and to other partners through its WW domain, proline-rich (PXXP) repeat and IPV (Ile-Pro-Val) motifs. Its intracellular expression can be induced by stressful stimuli, while is constitutive in skeletal muscle, cardiac myocytes and several tumour types. BAG3 can modulate the levels, localisation or activity of its partner proteins, thereby regulating major cell pathways and functions, including apoptosis, autophagy, mechanotransduction, cytoskeleton organisation, motility...
August 29, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28859986/kribb11-accelerates-mcl-1-degradation-through-an-hsf1-independent-mule-dependent-pathway-in-a549-non-small-cell-lung-cancer-cells
#9
Min-Jung Kang, Hye Hyeon Yun, Jeong-Hwa Lee
The Bcl-2 family protein, Mcl-1 is known to have anti-apoptotic functions, and depletion of Mcl-1 by cellular stresses favors the apoptotic process. Moreover, Mcl-1 levels are frequently increased in various cancer cells, including non-small cell lung cancer (NSCLC), and is implicated in resistance to conventional chemotherapy and in cancer metastasis. In this study, we demonstrated that KRIBB11 accelerates the proteasomal degradation of Mcl-1 in the NSCLC cell line, A549. While KRIBB11 is an inhibitor of HSF1, we found that KRIBB11 induced Mcl-1 degradation in an HSF1-independent manner...
October 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28808089/bag3-mediated-proteostasis-at-a-glance
#10
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
#11
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
#12
Tandekile Lubelwana Hafver, Pimthanya Wanichawan, Ornella Manfra, Gustavo Antonio de Souza, Marianne Lunde, Marita Martinsen, William Edward Louch, Ole Mathias Sejersted, Cathrine Rein Carlson
The sodium (Na(+) )-calcium (Ca(2+) ) exchanger 1 (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 MS 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 (where His is histidine) with His-trigger factor-NCX1cyt recombinant protein as bait...
September 2017: Proteomics
https://www.readbyqxmd.com/read/28737514/bag3-plays-a-central-role-in-proteostasis-in-the-heart
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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