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https://www.readbyqxmd.com/read/28439591/targeting-secondary-protein-complexes-in-drug-discovery-studying-the-druggability-and-chemical-biology-of-the-hsp70-bag1-complex
#1
Lindsay E Evans, Keith Jones, Matthew D Cheeseman
Proteins typically carry out their biological functions as multi-protein complexes, which can significantly affect the affinity of small-molecule inhibitors. HSP70 is an important target in oncology, so to study its chemical biology and the drug discovery potential of the HSP70/BAG1 complex, we designed a high-affinity non-nucleotide fluorescence polarisation probe.
April 25, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28424629/molecular-and-cellular-mechanisms-of-apoptosis-during-dissociated-spermatogenesis
#2
Tengfei Liu, Lingling Wang, Hong Chen, Yufei Huang, Ping Yang, Nisar Ahmed, Taozhi Wang, Yi Liu, Qiusheng Chen
Apoptosis is a tightly controlled process by which tissues eliminate unwanted cells. Spontaneous germ cell apoptosis in testis has been broadly investigated in mammals that have an associated spermatogenesis pattern. However, the mechanism of germ cell apoptosis in seasonally breeding reptiles following a dissociated spermatogenesis has remained enigmatic. In the present study, morphological evidence has clearly confirmed the dissociated spermatogenesis pattern in Pelodiscus sinensis. TUNEL and TEM analyses presented dynamic changes and ultrastructural characteristics of apoptotic germ cells during seasonal spermatogenesis, implying that apoptosis might be one of the key mechanisms to clear degraded germ cells...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28424560/an-exploratory-study-of-host-polymorphisms-in-genes-that-clinically-characterize-breast-cancer-tumors-and-pretreatment-cognitive-performance-in-breast-cancer-survivors
#3
Theresa A Koleck, Catherine M Bender, Beth Z Clark, Christopher M Ryan, Puja Ghotkar, Adam Brufsky, Priscilla F McAuliffe, Priya Rastogi, Susan M Sereika, Yvette P Conley
PURPOSE: Inspired by the hypothesis that heterogeneity in the biology of breast cancers at the cellular level may account for cognitive dysfunction symptom variability in survivors, the current study explored relationships between host single-nucleotide polymorphisms (SNPs) in 25 breast cancer-related candidate genes (AURKA, BAG1, BCL2, BIRC5, CCNB1, CD68, CENPA, CMC2, CTSL2, DIAPH3, ERBB2, ESR1, GRB7, GSTM1, MELK, MKI67, MMP11, MYBL2, NDC80, ORC6, PGR, RACGAP1, RFC4, RRM2, and SCUBE2), identified from clinically relevant prognostic multigene-expression profiles for breast cancer, and pretreatment cognitive performance...
2017: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28402699/inhibition-of-retrograde-transport-modulates-misfolded-protein-accumulation-and-clearance-in-motoneuron-diseases
#4
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
https://www.readbyqxmd.com/read/28358147/a-plant-bcl-2-associated-athanogene-is-proteolytically-activated-to-confer-fungal-resistance
#5
COMMENT
Mehdi Kabbage, Ryan Kessens, Martin B Dickman
The Bcl-2-associated athanogene (BAG) family is a multifunctional group of proteins involved in numerous cellular functions ranging from apoptosis to tumorigenesis. These proteins are evolutionarily conserved and encode a characteristic region known as the BAG domain. BAGs function as adapter proteins forming complexes with signaling molecules and molecular chaperones. In humans, a role for BAG proteins has been suggested in tumor growth, HIV infection, and neurodegenerative diseases; as a result, the BAGs are attractive targets for therapeutic interventions, and their expression in cells may serve as a predictive tool for disease development...
April 16, 2016: Microbial Cell
https://www.readbyqxmd.com/read/28303856/effect-of-matrix-metallopeptidase-13-on-the-function-of-mouse-bone-marrow-derived-dendritic-cells
#6
Xiao-Dong Li, Xin-Rui Zhang, Zhi-Hao Li, Yang Yang, Duo Zhang, Heng Zheng, Shu-Ying Dong, Juan Chen, Xian-Dong Zeng
BACKGROUND: Dendritic cells are professional antigen-presenting cells found in an immature state in epithelia and interstitial space, where they capture antigens such as pathogens or damaged tissue. Matrix metallopeptidase 13 (MMP-13), a member of the collagenase subfamily, is involved in many different cellular processes and is expressed in murine bone marrow-derived dendritic cells (DCs). The function of MMP-13 in DCs is not well understood. Here, we investigated the effect of MMP-13 on DC maturation, apoptosis, and phagocytosis...
March 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28266723/contribution-of-dopamine-neurotransmission-in-proconvulsant-effect-of-toxoplasma-gondii-infection-in-male-mice
#7
Jalal Babaie, Mohammad Sayyah, Pezhman Fard-Esfahani, Majid Golkar, Kourosh Gharagozli
Epilepsy is one of the most common neurologic disorders worldwide with no distinguishable cause in 60% of patients. One-third of world's population is infected with Toxoplasma gondii (T. gondii). This intracellular parasite has high tendency to excitable cells including neurons. We assessed seizure susceptibility and involvement of dopaminergic system in male mice with acute and chronic T. gondii infection. Mice were infected by intraperitoneal injection of T. gondii cysts. Acute and chronic stages of infection were determined by quantification of SAG1/BAG1 transcripts and level of repetitive REP-529 sequence in the brain of mice by real-time PCR...
March 7, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28251183/opposing-transcriptional-mechanisms-regulate-toxoplasma-development
#8
Dong-Pyo Hong, Joshua B Radke, Michael W White
The Toxoplasma biology that underlies human chronic infection is developmental conversion of the acute tachyzoite stage into the latent bradyzoite stage. We investigated the roles of two alkaline-stress-induced ApiAP2 transcription factors, AP2IV-3 and AP2IX-9, in bradyzoite development. These factors were expressed in two overlapping waves during bradyzoite development, with AP2IX-9 increasing expression earlier than AP2IV-3, which peaked as AP2IX-9 expression was declining. Disruption of the AP2IX-9 gene enhanced, while deletion of AP2IV-3 gene decreased, tissue cyst formation, demonstrating that these factors have opposite functions in bradyzoite development...
January 2017: MSphere
https://www.readbyqxmd.com/read/28165652/candidate-susceptibility-variants-for-esophageal-squamous-cell-carcinoma
#9
Iikki Donner, Riku Katainen, Tomas Tanskanen, Eevi Kaasinen, Mervi Aavikko, Kristian Ovaska, Miia Artama, Eero Pukkala, Lauri A Aaltonen
Esophageal cancer is common worldwide, and often fatal. The major histological subtype is esophageal squamous cell carcinoma (ESCC). ESCC shows familial aggregation and high heritability. Mutations in RHBDF2 cause tylosis, a very rare disorder characterized by high life-time risk of ESCC, but no other well-established predisposition genes have been identified. To identify candidate susceptibility variants for ESCC we utilized the Population Information System and the Finnish cancer registry to find study materials by clustering ESCC patients by family name at birth and municipality at birth...
February 6, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/27998983/bag1-co-chaperone-promotes-trc8-e3-ligase-dependent-degradation-of-misfolded-human-ether-a-go-go-related-gene-herg-potassium-channels
#10
Christine Hantouche, Brittany Williamson, William C Valinsky, Joshua Solomon, Alvin Shrier, Jason C Young
Cardiac long QT syndrome type 2 is caused by mutations in the human ether a go-go-related gene (hERG) potassium channel, many of which cause misfolding and degradation at the endoplasmic reticulum instead of normal trafficking to the cell surface. The Hsc70/Hsp70 chaperones assist the folding of the hERG cytosolic domains. Here, we demonstrate that the Hsp70 nucleotide exchange factor Bag1 promotes hERG degradation by the ubiquitin-proteasome system at the endoplasmic reticulum to regulate hERG levels and channel activity...
February 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27682262/rare-copy-number-alterations-and-copy-neutral-loss-of-heterozygosity-revealed-in-ameloblastomas-by-high-density-whole-genome-microarray-analysis
#11
Marina Gonçalves Diniz, Alessandra Pires Duarte, Rolando A Villacis, Bruna V A Guimarães, Luiz Cláudio Pires Duarte, Sílvia R Rogatto, Ricardo Santiago Gomez, Carolina Cavaliéri Gomes
BACKGROUND: Ameloblastoma (unicystic, UA, or multicystic, MA) is a rare tumor associated with bone destruction and facial deformity. Its malignant counterpart is the ameloblastic carcinoma (AC). The BRAFV600E mutation is highly prevalent in all these tumors subtypes and cannot account for their different clinical behaviors. METHODS: We assessed copy number alterations (CNAs) and copy-neutral loss of heterozygosity (cnLOH) in UA (n = 2), MA (n = 3), and AC (n = 1) using the CytoScan HD Array (Affymetrix) and the BRAFV600E status...
September 28, 2016: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/27633890/evaluation-of-paclitaxel-effects-in-the-pattern-of-expression-of-survival-and-apoptotic-genes-regulators-in-hela-cells
#12
Ugur Serbes, Ozlem D Ozsoylemez, Gul Ozcan
We aim to determine the regulation of apoptosis by paclitaxel-induced and understand cancer dynamics to treatment targets for HeLa cells by identifying decrease/increase genes expression on HeLa cells. In this study, the anti-tumor effects of Paclitaxel (PAC) on HeLa cells have been studied in order to determine the cellular and molecular mechanisms of these effects. PAC has been applied to HeLa cells in 6 different doses (3, 7.5, 15, 30, 60, 120 nM) for 48 hours and the IC50 dose MTT method, has been determined with apoptic index (AI) DAPI...
2016: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/27524912/two-gene-signature-improves-the-discriminatory-power-of-iaslc-ats-ers-classification-to-predict-the-survival-of-patients-with-early-stage-lung-adenocarcinoma
#13
Yifeng Sun, Likun Hou, Yu Yang, Huikang Xie, Yang Yang, Zhigang Li, Heng Zhao, Wen Gao, Bo Su
BACKGROUND: In this study, we investigated the contribution of a gene expression-based signature (composed of BAG1, BRCA1, CDC6, CDK2AP1, ERBB3, FUT3, IL11, LCK, RND3, SH3BGR) to survival prediction for early-stage lung adenocarcinoma categorized by the new International Association for the Study of Lung Cancer (IASLC)/the American Thoracic Society (ATS)/the European Respiratory Society (ERS) classification. We also aimed to verify whether gene signature improves the risk discrimination of IASLC/ATS/ERS classification in early-stage lung adenocarcinoma...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27514505/coinhibition-of-overexpressed-genes-in-acute-myeloid-leukemia-subtype-m2-by-gold-nanoparticles-functionalized-with-five-antisense-oligonucleotides-and-one-anti-cd33-cd34-aptamer
#14
M A Zaimy, A Jebali, B Bazrafshan, S Mehrtashfar, S Shabani, A Tavakoli, S H Hekmatimoghaddam, A Sarli, H Azizi, P Izadi, B Kazemi, A Shojaei, A Abdalaian, J Tavakkoly-Bazzaz
The aim of this study was to evaluate an engineered nanostructure to silence five important oncogenes, including BAG1, MDM2, Bcl-2, BIRC5 (survivin) and XIAP, in acute myeloid leukemia subtype 2 (AML-M2). The smart nanostructures were functionalized gold nanoparticles (FGNs) containing five antisense oligonucleotides (AOs) and one anti-CD33(+)/CD34(+) aptamer. First, the best AO for each gene was selected with the OligoWalk online software, and then different arrangements of AOs were evaluated with the RNAstructure software...
September 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27474739/non-canonical-interactions-between-heat-shock-cognate-protein-70-hsc70-and-bcl2-associated-anthanogene-bag-co-chaperones-are-important-for-client-release
#15
Jennifer N Rauch, Erik R P Zuiderweg, Jason E Gestwicki
Heat shock cognate protein 70 (Hsc70) regulates protein homeostasis through its reversible interactions with client proteins. Hsc70 has two major domains: a nucleotide-binding domain (NBD), that hydrolyzes ATP, and a substrate-binding domain (SBD), where clients are bound. Members of the BAG family of co-chaperones, including Bag1 and Bag3, are known to accelerate release of both ADP and client from Hsc70. The release of nucleotide is known to be mediated by interactions between the conserved BAG domain and the Hsc70 NBD...
September 16, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27162137/breaking-bag-the-co-chaperone-bag3-in-health-and-disease
#16
REVIEW
Christian Behl
Human BAG (Bcl-2-associated athanogene) proteins form a family of antiapoptotic proteins that currently consists of six members (BAG1-6) all sharing the BAG protein domain from which the name arises. Via this domain, BAG proteins bind to the heat shock protein 70 (Hsp70), thereby acting as a co-chaperone regulating the activity of Hsp70. In addition to their antiapoptotic activity, all human BAG proteins have distinct functions in health and disease, and BAG3 in particular is the focus of many investigations...
August 2016: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/27022301/identification-and-prioritization-of-candidate-genes-for-symptom-variability-in-breast-cancer-survivors-based-on-disease-characteristics-at-the-cellular-level
#17
Theresa A Koleck, Yvette P Conley
Research is beginning to suggest that the presence and/or severity of symptoms reported by breast cancer survivors may be associated with disease-related factors of cancer. In this article, we present a novel approach to the identification and prioritization of biologically plausible candidate genes to investigate relationships between genomic variation and symptom variability in breast cancer survivors. Cognitive dysfunction is utilized as a representative breast cancer survivor symptom to elucidate the conceptualization of and justification for our cellular, disease-based approach to address symptom variability in cancer survivors...
2016: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/26934577/exome-sequencing-of-oral-squamous-cell-carcinoma-in-users-of-arabian-snuff-reveals-novel-candidates-for-driver-genes
#18
Nezar Noor Al-Hebshi, Shiyong Li, Akram Thabet Nasher, Maged El-Setouhy, Rashad Alsanosi, Jan Blancato, Christopher Loffredo
The study sought to identify genetic aberrations driving oral squamous cell carcinoma (OSCC) development among users of shammah, an Arabian preparation of smokeless tobacco. Twenty archival OSCC samples, 15 of which with a history of shammah exposure, were whole-exome sequenced at an average depth of 127×. Somatic mutations were identified using a novel, matched controls-independent filtration algorithm. CODEX and Exomedepth coupled with a novel, Database of Genomic Variant-based filter were employed to call somatic gene-copy number variations...
July 15, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/26928609/induction-of-autophagy-interferes-the-tachyzoite-to-bradyzoite-transformation-of-toxoplasma-gondii
#19
Xiangzhi Li, Di Chen, Qianqian Hua, Yujing Wan, Lina Zheng, Yangyang Liu, Jiaxin Lin, Changwang Pan, Xin Hu, Feng Tan
Autophagy process in Toxoplasma gondii plays a vital role in regulating parasite survival or death. Thus, once having an understanding of certain effects of autophagy on the transformation of tachyzoite to bradyzoite this will allow us to elucidate the function of autophagy during parasite development. Herein, we used three TgAtg proteins involved in Atg8 conjugation system, TgAtg3, TgAtg7 and TgAtg8 to evaluate the autophagy level in tachyzoite and bradyzoite of Toxoplasma in vitro based on Pru TgAtg7-HA transgenic strains...
April 2016: Parasitology
https://www.readbyqxmd.com/read/26893680/role-of-bcl2-associated-athanogene-in-resistance-to-platinum-based-chemotherapy-in-non-small-cell-lung-cancer
#20
Yadi Wang, Minwen Ha, Jingsong Liu, Ping Li, Wenlu Zhang, Xuan Zhang
The present study aimed to address the pharmacogenetic role of BAG1 in platinum-based chemotherapy in advanced non-small-cell lung cancer (NSCLC) and in cultured human lung adenocarcinoma A549 cells. A total of 108 NSCLC patients (stages I-IIIA) were treated with a standard chemotherapy regimen of cisplatin plus vinorelbine. Additionally, in vitro cultured A549 cells were treated with cisplatin in the presence or absence of tunicamycin. Cell proliferation was determined by MTT assay and protein levels were assessed via western blot analysis...
February 2016: Oncology Letters
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