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https://www.readbyqxmd.com/read/28718450/dynamics-and-energetics-of-the-mammalian-phosphatidylinositol-transfer-protein-phospholipid-exchange-cycle
#1
Aby Grabon, Adam Orlowski, Ashutosh Tripathi, Joni Vuorio, Matti Javanainen, Tomasz Róg, Max Lönnfors, Mark I McDermott, Garland Siebert, Pentti Somerharju, Ilpo Vattulainen, Vytas A Bankaitis
Phosphatidylinositol-transfer proteins (PITPs) regulate phosphoinositide signaling in eukaryotic cells. The defining feature of PITPs is their ability to exchange phosphatidylinositol (PtdIns) molecules between membranes, and this property is central to PITP-mediated regulation of lipid signaling. Yet, the details of the PITP-mediated lipid exchange cycle remain entirely obscure. Here, all-atom molecular dynamics (MD) simulations of the mammalian StART-like PtdIns/ phosphatidylcholine (PtdCho) transfer protein PITPα, both on membrane bilayers and in solvated systems, informed downstream biochemical analyses that tested key aspects of the hypotheses generated by the MD simulations...
July 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28717943/a-pyrrole-based-natural-small-molecule-mitigates-hsp90-expression-in-mda-mb-231-cells-and-inhibits-tumor-angiogenesis-in-mice-by-inactivating-hsf-1
#2
K C Rashmi, H S Atreya, M Harsha Raj, Bharathi P Salimath, H S Aparna
Heat shock proteins (HSPs), molecular chaperones, are crucial for the cancer cells to facilitate proper functioning of various oncoproteins involved in cell survival, proliferation, migration, and tumor angiogenesis. Tumor cells are said to be "addicted" to HSPs. HSPs are overexpressed in many cancers due to upregulation of transcription factor Heat-shock factor 1 (HSF-1), the multifaceted master regulator of heat shock response. Therefore, pharmacological targeting of HSPs via HSF-1 is an effective strategy to treat malignant cancers like triple negative breast cancer...
July 17, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28715732/proteasome-inhibitor-induced-cleavage-of-hsp90-is-mediated-by-ros-generation-and-caspase-10-activation-in-human-leukemic-cells
#3
Sangkyu Park, Jeong-A Park, Hwanmin Yoo, Han-Bum Park, Younghee Lee
Heat shock protein 90 (HSP90) is a molecular chaperone that supports the stability of client proteins. The proteasome is one of the targets for cancer therapy, and studies are underway to use proteasome inhibitors as anti-cancer drugs. In this study, we found that HSP90 was cleaved to a 55kDa protein after treatment with proteasome inhibitors including MG132 in leukemia cells but was not cleaved in other tissue-derived cells. HSP90 has two major isoforms (HSP90α and HSP90β), and both were cleaved by MG132 treatment...
July 12, 2017: Redox Biology
https://www.readbyqxmd.com/read/28715601/methamphetamine-increases-prion-protein-and-induces-dopamine-dependent-expression-of-protease-resistant-prpsc
#4
M Ferrucci, L Ryskalin, F Biagioni, S Gambardella, C L Busceti, A Falleni, G Lazzeri, F Fornai
The cellular prion protein (PrPc) is physiologically expressed within selective brain areas of mammals. Alterations in the secondary structure of this protein lead to scrapie-like prion protein (PrPsc), which precipitates in the cell. PrPsc has been detected in infectious, inherited or sporadic neurodegenerative disorders. Prion protein metabolism is dependent on autophagy and ubiquitin proteasome. Despite not being fully elucidated, the physiological role of prion protein relates to chaperones which rescue cells under stressful conditions...
July 1, 2017: Archives Italiennes de Biologie
https://www.readbyqxmd.com/read/28715410/cloning-of-hsp90-expression-and-localization-of-hsp70-90-in-different-tissues-including-lactating-non-lactating-yak-bos-grunniens-breast-tissue
#5
Penggang Liu, Sijiu Yu, Yan Cui, Junfeng He, Chuan Yu, Zexing Wen, Yangyang Pan, Kun Yang, Liangli Song, Xue Yang
The aim of this study is to investigate the expression and localization of HSP70/90 in different tissues and explore the regulation effects of HSP70/90 at lactation period of female yaks. HSP90 mRNA was cloned from the heart samples of female yaks, Quantitative real-time (qRT-PCR), Western blotting (WB), immunohistochemistry and immunofluorescence assays were utilized to analyze the expressions of HSP70/90 mRNA and protein in different tissues. Sequence analysis showed that HSP90 is a conserved molecular chaperone of female yaks...
2017: PloS One
https://www.readbyqxmd.com/read/28714602/genome-wide%C3%A2-identification-and-characterization%C3%A2-of%C3%A2-hsp-gene-superfamily-in-whitefly-bemisia-tabaci-and-expression-profiling%C3%A2-analysis%C3%A2-under-temperature-stress
#6
Xin-Ru Wang, Chao Wang, Fei-Xue Ban, Dan-Tong Zhu, Shu-Sheng Liu, Xiao-Wei Wang
Heat shock proteins (Hsp) are essential molecular chaperones that play important roles in the stress stimulation of insects. Bemisia tabaci, a phloem feeder and invasive species, can cause extensive crop damage through direct feeding and transmission of plant viruses. Here we employed comprehensive genomics approaches to identity HSP superfamily members in Middle East Asia Minor 1 whitefly genome. In total, we identified 26 Hsp genes, including 3 Hsp90, 17 Hsp70, 1 Hsp60 and 5 sHSP (small heat shock protein, sHSP) genes...
July 17, 2017: Insect Science
https://www.readbyqxmd.com/read/28713903/hsp90-inhibitor-induces-kg-1a-cell-differentiation-and-apoptosis-via-akt-nf-%C3%AE%C2%BAb-signaling
#7
Jin-Hong Qin, Kun Wang, Xin-Lu Fu, Peng-Jun Zhou, Zhong Liu, Dan-Dan Xu, Yi-Fei Wang, De-Po Yang, Qiu-Ling Xie, Qiu-Ying Liu
Heat-shock protein 90 (Hsp 90) acts as a molecular chaperone that maintains protein stability and regulates cell proliferation, survival, differentiation and apoptosis. The present study investigated the effect of Hsp90 inhibition on human acute myeloid leukemia (AML) cells using the novel small-molecule inhibitor SNX-2112. We found that SNX-2112 more potently inhibited KG-1a cell growth than the classical Hsp90 inhibitor 17-(2-dimethylaminoethyl)amino‑17-demethoxygeldanamycin as determined by CCK-8 assay...
July 7, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28711525/novel-hsp90-inhibitor-platycodin-d-disrupts-hsp90-cdc37-complex-and-enhances-the-anticancer-effect-of-mtor-inhibitor
#8
Ting Li, Xin Chen, Xiao-Yang Dai, Bin Wei, Qin-Jie Weng, Xiuping Chen, De-Fang Ouyang, Ru Yan, Zhang-Jian Huang, Hu-Lin Jiang, Hong Zhu, Jin-Jian Lu
Heat shock protein 90 (Hsp90) is a critically conserved molecular chaperone protein and promising therapeutic target for cancer treatment. In this study, platycodin D (PD), a saponin isolated from traditional Chinese herb Platycodonis Radix, was identified as a novel Hsp90 inhibitor. We verified that PD did not affect the ATPase activity of Hsp90. However, PD disrupted the co-chaperone interaction of Hsp90/cell division cycle protein 37 (Cdc37) and subsequently degraded multiple Hsp90 client proteins without the feedback increase of Hsp70...
July 12, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28710113/trap1-ameliorates-renal-tubulointerstitial-fibrosis-in-mice-with-unilateral-ureteral-obstruction-by-protecting-renal-tubular-epithelial-cell-mitochondria
#9
Jun-Feng Chen, Qi-Shun Wu, Yu-Xian Xie, Bo-Lin Si, Ping-Ping Yang, Wen-Yan Wang, Qin Hua, Qing He
Mitochondrial dysfunction causes renal tubular epithelial cell injury and promotes cell apoptosis and renal tubulointerstitial fibrosis (TIF) progression. TNF receptor-associated protein 1 (TRAP1) is a molecular chaperone protein that is localized in mitochondria. It plays an important role in cell apoptosis; however, its functional mechanism in TIF remains unclear. In this study, we observed the effects of TRAP1 in renal tubular epithelial cell mitochondria in mice with unilateral ureteral obstruction and its function in cell apoptosis and TIF...
July 14, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28708980/cd3-cd28-dynabeads-induce-expression-of-tn-antigen-in-human-t-cells-accompanied-by-hypermethylation-of-the-cosmc-promoter
#10
Chuanqin Shi, Xue Xu, Xiaofeng Yu, Zhenzhen Du, Xiying Luan, Dachang Liu, Tao Hu
Glycosylation is an important protein post-translational modification. In this process, the intermediate product, Tn antigen, arises from somatic mutations in core1β3-galactosyltransferase-specific molecular chaperone (Cosmc), which is required for the formation of active core1β3-galactosyltransferase (T-synthase). As a type of tumor-associated carbohydrate antigen, Tn antigen is mainly expressed in many human tumor cells and is absent in normal cells. Surprisingly, it is also expressed in normal activated T cells after in vitro stimulation, but the mechanism underlying its expression remains unclear...
July 11, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28707656/-regulation-of-heat-shock-gene-expression-in-response-to-stress
#11
D G Garbuz
Heat shock (HS) genes, or stress genes, code for a number of proteins that collectively form the most ancient and universal stress defense system. The system determines the cell capability of adaptation to various adverse factors and performs a variety of auxiliary functions in normal physiological conditions. Common stress factors, such as higher temperatures, hypoxia, heavy metals, and others, suppress transcription and translation for the majority of genes, while HS genes are upregulated. Transcription of HS genes is controlled by transcription factors of the HS factor (HSF) family...
May 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28706332/role-of-elsholtzia-communis-in-counteracting-stress-by-modulating-expression-of-hspa14-c-ebp-homologous-protein-nuclear-factor-erythroid-derived-2-like-2-factor-caspase-3-and-brain-derived-neurotrophic-factor-in-rat-hippocampus
#12
Chandana Choudhury Barua, Pompy Patowary, Arundhati Purkayastha, Prakash Haloi, Manab Jyoti Bordoloi
OBJECTIVE: Elsholtzia communis (Collett and Hemsl.) Diels has been widely distributed and is reported for many therapeutic effects. The present study aims to investigate the antistress activity of the leaf extract and its possible molecular mechanism. MATERIALS AND METHODS: Hydroethanolic extract of leaves of E. communis (100 and 200 mg/kg, p.o.) were administered for 7 days to stress-induced male Wistar rats. The experimental animals were divided into five groups (n = 6)...
March 2017: Indian Journal of Pharmacology
https://www.readbyqxmd.com/read/28706146/ros-independent-nrf2-activation-in-prostate-cancer
#13
Ilaria Bellezza, Paolo Scarpelli, Salvatore V Pizzo, Silvia Grottelli, Egidia Costanzi, Alba Minelli
In prostate cancer, oxidative stress and the subsequent Nrf2 activation promote the survival of cancer cells and acquired chemoresistance. Nrf2 links prostate cancer to endoplasmic reticulum stress, an event that triggers the unfolded protein response, aiming to restore cellular homeostasis as well as an adaptive survival mechanism. Glucose-regulated protein of 78 kD /immunoglobulin heavy chain binding protein (GRP78/BiP) is a key molecular chaperone in the endoplasmic reticulum that, when expressed at the cell surface, acts as a receptor for several signaling pathways enhancing antiapoptotic and proliferative signals...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28704199/the-role-of-ubiquitin-proteasomal-system-and-autophagy-lysosome-pathway-in-alzheimer-s-disease
#14
Yuan Zhang, Xu Chen, Yanfang Zhao, Murugavel Ponnusamy, Ying Liu
Alzheimer's disease (AD) is the most common neurodegenerative disorder leading to dementia in the elderly population. AD is associated with the buildup of β-amyloid and tau, which aggregate into extracellular plaques and neurofibrillary tangles. Although the exact mechanism of pathological process of AD is unclear, the dysfunction of protein degradation mechanisms has been proposed to play an important role in AD. The cellular degradation of abnormal or misfolded proteins consists of three different mechanisms: the ubiquitin proteasomal system (UPS), autophagy-lysosomal pathway (ALP), and interaction of molecular chaperones with UPS or ALP...
July 12, 2017: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/28701379/loss-of-clusterin-shifts-amyloid-deposition-to-the-cerebrovasculature-via-disruption-of-perivascular-drainage-pathways
#15
Aleksandra M Wojtas, Silvia S Kang, Benjamin M Olley, Maureen Gatherer, Mitsuru Shinohara, Patricia A Lozano, Chia-Chen Liu, Aishe Kurti, Kelsey E Baker, Dennis W Dickson, Mei Yue, Leonard Petrucelli, Guojun Bu, Roxana O Carare, John D Fryer
Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) peptide deposition in brain parenchyma as plaques and in cerebral blood vessels as cerebral amyloid angiopathy (CAA). CAA deposition leads to several clinical complications, including intracerebral hemorrhage. The underlying molecular mechanisms that regulate plaque and CAA deposition in the vast majority of sporadic AD patients remain unclear. The clusterin (CLU) gene is genetically associated with AD and CLU has been shown to alter aggregation, toxicity, and blood-brain barrier transport of Aβ, suggesting it might play a key role in regulating the balance between Aβ deposition and clearance in both brain and blood vessels...
July 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28700685/characterization-of-the-molecular-chaperone-clpb-from-the-pathogenic-spirochaete-leptospira-interrogans
#16
Joanna Krajewska, Anna Modrak-Wójcik, Zbigniew J Arent, Daniel Więckowski, Michal Zolkiewski, Agnieszka Bzowska, Sabina Kędzierska-Mieszkowska
Leptospira interrogans is a spirochaete responsible for leptospirosis in mammals. The molecular mechanisms of the Leptospira virulence remain mostly unknown. Recently, it has been demonstrated that an AAA+ chaperone ClpB (a member of the Hsp100 family) from L. interrogans (ClpBLi) is not only essential for survival of Leptospira under the thermal and oxidative stresses, but also during infection of a host. The aim of this study was to provide further insight into the role of ClpB in the pathogenic spirochaetes and explore its biochemical properties...
2017: PloS One
https://www.readbyqxmd.com/read/28700604/molecular-characterization-of-the-acquisition-of-longevity-during-seed-maturation-in-soybean
#17
Juliana Joice Pereira Lima, Julia Buitink, David Lalanne, Rubiana Falopa Rossi, Sandra Pelletier, Edvaldo Aparecido Amaral da Silva, Olivier Leprince
Seed longevity, defined as the ability to remain alive during storage, is an important agronomic factor. Poor longevity negatively impacts seedling establishment and consequently crop yield. This is particularly problematic for soybean as seeds have a short lifespan. While the economic importance of soybean has fueled a large number of transcriptome studies during embryogenesis and seed filling, the mechanisms regulating seed longevity during late maturation remain poorly understood. Here, a detailed physiological and molecular characterization of late seed maturation was performed in soybean to obtain a comprehensive overview of the regulatory genes that are potentially involved in longevity...
2017: PloS One
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/28699903/molecular-chaperones-in-the-acquisition-of-cancer-cell-chemoresistance-with-mutated-tp53-and-mdm2-up-regulation
#19
Zuzanna Tracz-Gaszewska, Marta Klimczak, Przemyslaw Biecek, Marcin Herok, Marcin Kosinski, Maciej B Olszewski, Patrycja Czerwińska, Milena Wiech, Maciej Wiznerowicz, Alicja Zylicz, Maciej Zylicz, Bartosz Wawrzynow
Utilizing the TCGA PANCAN12 dataset we discovered that cancer patients with mutations in TP53 tumor suppressor and overexpression of MDM2 oncogene exhibited decreased survival post treatment. Interestingly, in the case of breast cancer patients, this phenomenon correlated with high expression level of several molecular chaperones belonging to the HSPA, DNAJB and HSPC families. To verify the hypothesis that such a genetic background may promote chaperone-mediated chemoresistance, we employed breast and lung cancer cell lines that constitutively overexpressed heat shock proteins and have shown that HSPA1A/HSP70 and DNAJB1/HSP40 facilitated the binding of mutated p53 to the TAp73α protein...
June 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28699655/repair-or-destruction-an-intimate-liaison-between-ubiquitin-ligases-and-molecular-chaperones-in-proteostasis
#20
REVIEW
Éva Kevei, Wojciech Pokrzywa, Thorsten Hoppe
Cellular differentiation, developmental processes, and environmental factors challenge the integrity of the proteome in every eukaryotic cell. The maintenance of protein homeostasis, or proteostasis, involves folding and degradation of damaged proteins, and is essential for cellular function, organismal growth, and viability [1, 2]. Misfolded proteins that cannot be refolded by chaperone machineries are degraded by specialized proteolytic systems. A major degradation pathway regulating cellular proteostasis is the ubiquitin/proteasome-system (UPS), which regulates turnover of damaged proteins that accumulate upon stress and during aging...
July 12, 2017: FEBS Letters
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