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Linlin Bi, Qian Yang, Jiani Yuan, Qing Miao, Linrui Duan, Feng Li, Siwang Wang
In the present study, the tumor-suppressive role of microRNA-127-3p (miR-127-3p) in epithelial ovarian cancer (EOC) was elucidated. Expression of miR-127-3p was examined by quantitative RT-PCR (qRT-PCR) in 9 EOC cell lines and clinical samples from 13 EOC patients. EOC cell lines, OVCAR-3 and Caov-3, were transduced with a lentivirus to overexpress endogenous miR-127-3p. The tumor-suppressive effects of miR-127-3p on EOC proliferation, bufalin sensitivity, invasion and in vivo growth were investigated through proliferation, bufalin sensitivity wound-closure and in vivo tumorigenicity assays, respectively...
August 29, 2016: Oncology Reports
Yuan Yu, Lei Liu, Ruirui Ma, Haibing Gong, Ping Xu, Congjun Wang
Pancreatic carcinoma is one of the most malignant human cancers. In this study, we intended to explore the molecular functional of microRNA-127 (miR-127) in regulating pancreatic cancer development both in vitro and in vivo. Quantitative real-time PCR (qRT-PCR) was performed to evaluate endogenous miR-127 expression in in vitro pancreatic cancer cell lines and in vivo clinical samples of pancreatic carcinoma. Lentiviral technology was applied to overexpress miR-127 in capan-1 and PANC-1 cells. Pancreatic cancer proliferation, cell-cycle progression, and invasion were assessed in vitro, and capan-1-derived tumorigenicity was evaluated in vivo...
August 29, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Luhua Li, Yangfei Xing, Dong Chang, Shasha Fang, Boyang Cui, Qi Li, Xuejie Wang, Shang Guo, Xue Yang, Shuzhen Men, Yuequan Shen
Calcium signaling plays an essential role in plant cell physiology, and chaperone-mediated protein folding directly regulates plant programmed cell death. The Arabidopsis thaliana protein AtBAG5 (Bcl-2-associated athanogene 5) is unique in that it contains both a BAG domain capable of binding Hsc70 (Heat shock cognate protein 70) and a characteristic IQ motif that is specific for Ca(2+)-free CaM (Calmodulin) binding and hence acts as a hub linking calcium signaling and the chaperone system. Here, we determined crystal structures of AtBAG5 alone and in complex with Ca(2+)-free CaM...
2016: Scientific Reports
Rodrigo Prandini da Costa Reis, Robin Crisman, Margie Roser, Richard Malik, Jan Šlapeta
Neonatal neosporosis is a challenging disease to diagnose in neonatal and young puppies because the first signs of this condition may not be strongly suggestive of an infectious aetiology. Within two weeks of birth, three of four pups died with a subacute clinical course, some with dyspnea, some with diarrhoea and some with neurologic signs. Neosporosis was diagnosed post-mortem, but only after microscopic examination of tissues collected at necropsy. Histological findings consisted of (i) necrotizing, diffuse interstitial pneumonia associated with intralesional protozoa and (ii) necrotizing multifocal myocarditis with mineralization and intralesional protozoa...
May 15, 2016: Veterinary Parasitology
Boyang Cui, Shasha Fang, Yangfei Xing, Yuequan Shen, Xue Yang
Arabidopsis thaliana BAG5 (AtBAG5) belongs to the plant BAG (Bcl-2-associated athanogene) family that performs diverse functions ranging from growth and development to abiotic stress and senescence. BAG family members can act as nucleotide-exchange factors for heat-shock protein 70 (Hsp70) through binding of their evolutionarily conserved BAG domains to the Hsp70 ATPase domain, and thus may be involved in the regulation of chaperone-mediated protein folding in plants. AtBAG5 is distinguished from other family members by the presence of a unique IQ motif adjacent to the BAG domain; this motif is specific for calmodulin (CaM) binding, indicating a potential role in the plant calcium signalling pathway...
July 2015: Acta Crystallographica. Section F, Structural Biology Communications
Ke Guo, Liuhong Li, Gang Yin, Xiaohong Zi, Lei Liu
The pathological mechanism of Alzheimer's disease (AD) needs to be elucidated. The Bcl-2 associated athanogene 5 (Bag5) is an important member in the Bag family. However, the role of Bag5 in AD has not yet been elucidated. In this study, we found that expression of Bag5 is elevated in the brains of AD transgenic Tg2576 mice at both mRNA levels and proteins. In vitro experiments indicated that Aβ1-42 treatment led to the upregulation of Bag5 in a dose-dependent manner. In addition, our results indicated that inhibition of Bag5 using small RNA interferences exacerbated Aβ1-42-induced neurotoxicity...
April 2015: Journal of Molecular Neuroscience: MN
Xiang-Qian Che, Bei-Sha Tang, Hong-Feng Wang, Xin-Xiang Yan, Hong Jiang, Lu Shen, Qian Xu, Guang-Hui Wang, Hai-Nan Zhang, Chun-Yu Wang, Ji-Feng Guo
The expansion of a polyglutamine domain in the protein ataxin3 causes spinocerebellar ataxia type-3 (SCA3). However, there is little information to date about the upstream proteins in the ubiquitin-proteasome system of pathogenic ataxin3-80Q. Here, we report that BAG2 (Bcl-2 associated athanogene family protein 2) and BAG5 (Bcl-2-associated athanogene family protein 5) stabilise pathogenic ataxin3-80Q by inhibiting its ubiquitination as determined based on western blotting and co-immunofluorescence experiments...
May 2015: International Journal of Neuroscience
Xuejing Wang, Jifeng Guo, Erkang Fei, Yingfeng Mu, Shuang He, Xiangqian Che, Jieqiong Tan, Kun Xia, Zhuohua Zhang, Guanghui Wang, Beisha Tang
Mutations in PTEN-induced kinase 1 (PINK1) gene cause PARK6 familial Parkinsonism, and loss of the stability of PINK1 may also contribute to sporadic Parkinson's disease (PD). Degradation of PINK1 occurs predominantly through the ubiquitin proteasome system (UPS), however, to date, few of the proteins have been found to regulate the degradation of PINK1. Using the yeast two-hybrid system and pull-down methods, we identified bcl-2-associated athanogene 5 (BAG5), a BAG family member, directly interacted with PINK1...
2014: PloS One
Zhang Ying, Gao Haiyan, Gao Haidong
The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor-suppressing lipid phosphatase that is frequently absent in breast tumors. Thus, the stability of PTEN is essential for tumor prevention and therapy. The ubiquitin-proteasome pathway has an important role in regulating the functions of PTEN. Specifically, carboxyl terminus Hsp70-interacting protein (CHIP), the E3 ubiquitin ligase of PTEN, can regulate PTEN levels. In this study, we report that BCL-2-associated athanogene 5 (BAG5), a known inhibitor of CHIP activity, reduces the degradation of PTEN and maintains its levels via an ubiquitylation-dependent pathway...
October 2013: BMB Reports
Anja Bruchmann, Corinna Roller, Tamara Vanessa Walther, Georg Schäfer, Sara Lehmusvaara, Tapio Visakorpi, Helmut Klocker, Andrew C B Cato, Danilo Maddalo
BACKGROUND: The Bag (Bcl-2 associated athanogene) family of proteins consists of 6 members sharing a common, single-copied Bag domain through which they interact with the molecular chaperone Hsp70. Bag5 represents an exception in the Bag family since it consists of 5 Bag domains covering the whole protein. Bag proteins like Bag1 and Bag3 have been implicated in tumor growth and survival but it is not known whether Bag5 also exhibits this function. METHODS: Bag5 mRNA and protein expression levels were investigated in prostate cancer patient samples using real-time PCR and immunoblot analyses...
2013: BMC Cancer
Mingming Ma, Xuejing Wang, Xuebing Ding, Jing Jing, Yaohua Ma, Junfang Teng
OBJECTIVES: Parkinson's disease (PD) is the most common neurodegenerative disease in humans, and an abundance of evidence has implicated apoptosis signaling pathways in the neurodegeneration of PD. The purpose of this study was to assess the role of B-cell lymphoma 2 (Bcl-2)-associated athanogene 5 (BAG5) protein, which was previously confirmed to play an important role in the pathogenesis of PD, in the regulation of apoptosis induced by 1-methyl-4-phenyl-pyridinium (MPP(+)) in PC12 cells...
December 2012: Neurological Research
Ronan Rogers, Moyez Dharsee, Suzanne Ackloo, John G Flanagan
PURPOSE: To determine protein regulation following activation of human, optic nerve head (ONH), lamina cribrosa (LC) cells in response to mechanical strain. METHODS: LC cells were isolated and grown from donor tissue in specific media at 37°C and 5% CO(2) humidified incubator. Cells were grown to confluence on collagen I-coated flexible-bottom culture plates, rinsed with Dulbecco's phosphate-buffered saline, and left for 24 hours in serum-free media. They were subjected to 3% or 12% cyclic equiaxial stretch for 2 or 24 hours using a commercial strain-unit system...
June 2012: Investigative Ophthalmology & Visual Science
Lorraine V Kalia, Suneil K Kalia, Hien Chau, Andres M Lozano, Bradley T Hyman, Pamela J McLean
Parkinson's disease (PD) is a common neurodegenerative condition in which abnormalities in protein homeostasis, or proteostasis, may lead to accumulation of the protein α-synuclein (α-syn). Mutations within or multiplications of the gene encoding α-syn are known to cause genetic forms of PD and polymorphisms in the gene are recently established risk factors for idiopathic PD. α-syn is a major component of Lewy bodies, the intracellular proteinaceous inclusions which are pathological hallmarks of most forms of PD...
2011: PloS One
Xuejing Wang, Jifeng Guo, Hong Jiang, Lu Shen, Beisha Tang
OBJECTIVE: To explore the interaction between BCL2-associated athanogene 5 (BAG5) and Parkin protein,and the regulatory mechanism of BAG5 protein on the level of Parkin protein. METHODS: We performed GST pull-down assay to identify which domain of PINK1 interacted with Parkin, and generated different deletions of BAG5 to identify the domains. Chase time experiment was done to determine the effect of co-regulation of BAG5 protein on the ubiquitination. We further examined the possible interaction between Parkin and PINK1 in 293A cells by co-immunoprecipitation method...
November 2010: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
S K Kalia, L V Kalia, P J McLean
Parkinson's disease is a neurodegenerative movement disorder that is caused, in part, by the loss of dopaminergic neurons within the substantia nigra pars compacta of the basal ganglia. The presence of intracellular protein aggregates, known as Lewy bodies and Lewy neurites, within the surviving nigral neurons is the defining neuropathological feature of the disease. Accordingly, the identification of specific genes mutated in families with Parkinson's disease and of genetic susceptibility variants for idiopathic Parkinson's disease has implicated abnormalities in proteostasis, or the handling and elimination of misfolded proteins, in the pathogenesis of this neurodegenerative disorder...
December 2010: CNS & Neurological Disorders Drug Targets
Jennifer L Kelly, Anne J Novak, Zachary S Fredericksen, Mark Liebow, Stephen M Ansell, Ahmet Dogan, Alice H Wang, Thomas E Witzig, Timothy G Call, Neil E Kay, Thomas M Habermann, Susan L Slager, James R Cerhan
BACKGROUND: The t(14;18)(q32;q21) translocation is the most commonly observed chromosomal translocation in non-Hodgkin's lymphoma (NHL), resulting in constitutive Bcl-2 expression and apoptosis inhibition. In addition, germline variation in both BCL2L11 (BIM) and CASP9, known regulators of apoptosis, has recently been linked to NHL risk. We conducted a comprehensive evaluation of 36 apoptosis pathway genes with risk of NHL. METHODS: We genotyped 226 single-nucleotide polymorphisms (SNP) from 36 candidate genes in a clinic-based study of 441 newly diagnosed NHL cases and 475 frequency-matched controls...
November 2010: Cancer Epidemiology, Biomarkers & Prevention
Akihiko Arakawa, Noriko Handa, Noboru Ohsawa, Meiri Shida, Takanori Kigawa, Fumiaki Hayashi, Mikako Shirouzu, Shigeyuki Yokoyama
ADP-ATP exchange by the molecular chaperone Hsp70 is enhanced by several cochaperones. BAG5 consists of five BAG domains and associates with the nucleotide-binding domain (NBD) of Hsp70. The overexpression of BAG5 in the cytosol reportedly disturbs Hsp70-mediated protein refolding and induces Parkinson's disease. In the present study, we found that the fifth BAG domain (BD5) of BAG5 is responsible for the interaction between Hsp70 and BAG5. We also determined the crystal structures of the BD5*NBD complex. BD5 binding caused two different types of NBD conformational changes, which both disrupted the nucleotide-binding groove...
March 10, 2010: Structure
Adrien Daigeler, Christina Brenzel, Daniel Bulut, Anne Geisler, Christoph Hilgert, Marcus Lehnhardt, Hans U Steinau, Annegret Flier, Lars Steinstraesser, Ludger Klein-Hitpass, Ulrich Mittelkötter, Waldemar Uhl, Ansgar M Chromik
BACKGROUND: Disseminated soft tissue sarcoma still represents a therapeutic dilemma because effective cytostatics are missing. Therefore we tested TRAIL and Tarolidine (TRD), two substances with apoptogenic properties on human fibrosarcoma (HT1080). METHODS: Viability, apoptosis and necrosis were visualized by TUNEL-Assay and quantitated by FACS analysis (Propidiumiodide/AnnexinV staining). Gene expression was analysed by RNA-Microarray and the results validated for selected genes by rtPCR...
2008: Journal of Experimental & Clinical Cancer Research: CR
Xiao-ye Zheng, Mei Yang, Jie-qiong Tan, Qian Pan, Zhi-gao Long, He-ping Dai, Kun Xia, Jia-hui Xia, Zhuo-hua Zhang
OBJECTIVE: To isolate and identify the potential binding partners of LRRK2, a gene linked to both dominant familial form and sporadic form of Parkinson's disease, thus to further our knowledge of its function. METHODS: We used a sequence containing full-length of COR domain and part of ROC and MAPKKK domain as bait. The bait amplified by polymerase chain reaction (PCR) was then cloned into a yeast expression plasmid pGBKT7. After being sequenced and analyzed, pGBKT7-bait was transformed into the yeast strain AH109...
October 2008: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
Rita Sarközi, Paul Perco, Kathrin Hochegger, Julia Enrich, Martin Wiesinger, Markus Pirklbauer, Susanne Eder, Michael Rudnicki, Alexander R Rosenkranz, Bernd Mayer, Gert Mayer, Herbert Schramek
Bortezomib has been introduced recently in the therapy of multiple myeloma (MM), a disease that is frequently associated with progressive renal failure. Because bortezomib-based therapy has been reported to lead to a rapid recovery of kidney function in patients with MM, we decided to study its direct effects in proximal tubular epithelial cells (PTCs) compared with glomerular mesangial cells (GMCs). After 24 h of stimulation, 50 nM bortezomib led to a 6.37-fold induction of apoptosis and markedly activated caspase-9 and -3 in GMCs but not in PTCs...
December 2008: Journal of Pharmacology and Experimental Therapeutics
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