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https://www.readbyqxmd.com/read/29206917/tunicamycin-induced-er-stress-in-breast-cancer-cells-neither-expresses-grp78-on-the-surface-nor-secretes-it-into-the-media
#1
Jesús E Serrano-Negrón, Zhenbo Zhang, Andrea P Rivera-Ruiz, Aditi Banerjee, Eva C Romero-Nutz, Neysharie Sánchez-Torres, Krishna Baksi, Dipak K Banerjee
GRP78 (an Mr 78 kDa calcium dependent glucose binding protein) located in ER lumen. It functions as ER chaperone and translocates proteins for glycosylation at the asparagine residue present in the sequon Asn-X-Ser/Thr. Paraffin sections from N-glycosylation inhibitor tunicamycin treated ER-/PR-/HER2+ (double negative) breast tumor in athymic nude mice exhibited reduced N-glycan but increased GRP78 expression. We have evaluated the effect of tunicamycin on cellular localization of GRP78 in metastatic human breast cancer cells MDA-MB-231 (ER-/PR-/HER2-)...
December 1, 2017: Glycobiology
https://www.readbyqxmd.com/read/29202016/inhibition-of-ngly1-inactivates-the-transcription-factor-nrf1-and-potentiates-proteasome-inhibitor-cytotoxicity
#2
Frederick M Tomlin, Ulla I M Gerling-Driessen, Yi-Chang Liu, Ryan A Flynn, Janakiram R Vangala, Christian S Lentz, Sandra Clauder-Muenster, Petra Jakob, William F Mueller, Diana Ordoñez-Rueda, Malte Paulsen, Naoko Matsui, Deirdre Foley, Agnes Rafalko, Tadashi Suzuki, Matthew Bogyo, Lars M Steinmetz, Senthil K Radhakrishnan, Carolyn R Bertozzi
Proteasome inhibitors are used to treat blood cancers such as multiple myeloma (MM) and mantle cell lymphoma. The efficacy of these drugs is frequently undermined by acquired resistance. One mechanism of proteasome inhibitor resistance may involve the transcription factor Nuclear Factor, Erythroid 2 Like 1 (NFE2L1, also referred to as Nrf1), which responds to proteasome insufficiency or pharmacological inhibition by upregulating proteasome subunit gene expression. This "bounce-back" response is achieved through a unique mechanism...
November 22, 2017: ACS Central Science
https://www.readbyqxmd.com/read/29168059/sec61%C3%AE-facilitates-the-maintenance-of-endoplasmic-reticulum-homeostasis-by-associating-microtubules
#3
Yimeng Zhu, Gangming Zhang, Shaoyu Lin, Juanming Shi, Hong Zhang, Junjie Hu
Sec61β, a subunit of the Sec61 translocon complex, is not essential in yeast and commonly used as a marker of endoplasmic reticulum (ER). In higher eukaryotes, such as Drosophila, deletion of Sec61β causes lethality, but its physiological role is unclear. Here, we show that Sec61β interacts directly with microtubules. Overexpression of Sec61β containing small epitope tags, but not a RFP tag, induces dramatic bundling of the ER and microtubule. A basic region in the cytosolic domain of Sec61β is critical for microtubule association...
November 22, 2017: Protein & Cell
https://www.readbyqxmd.com/read/29163222/an-update-on-sec61-channel-functions-mechanisms-and-related-diseases
#4
REVIEW
Sven Lang, Stefan Pfeffer, Po-Hsien Lee, Adolfo Cavalié, Volkhard Helms, Friedrich Förster, Richard Zimmermann
The membrane of the endoplasmic reticulum (ER) of nucleated human cells harbors the protein translocon, which facilitates membrane integration or translocation of almost every newly synthesized polypeptide targeted to organelles of the endo- and exocytotic pathway. The translocon comprises the polypeptide-conducting Sec61 channel and several additional proteins and complexes that are permanently or transiently associated with the heterotrimeric Sec61 complex. This ensemble of proteins facilitates ER targeting of precursor polypeptides, modification of precursor polypeptides in transit through the Sec61 complex, and Sec61 channel gating, i...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29152155/chibby-1-a-new-component-of-%C3%AE-catenin-signaling-in-chronic-myeloid-leukemia
#5
REVIEW
Manuela Mancini, Simona Soverini, Gabriele Gugliotta, Maria Alessandra Santucci, Gianantonio Rosti, Michele Cavo, Giovanni Martinelli, Fausto Castagnetti
Chibby 1 (CBY1) is a small and evolutionarily conserved protein, which act as β-catenin antagonist. CBY1 is encoded by C22orf2 (22q13.1) Its antagonistic function on β-catenin involves the direct interaction with: The C-terminal activation domain of β-catenin, which hinders β-catenin binding with Tcf/Lef transcription factors hence repressing β-catenin transcriptional activation. 14-3-3 scaffolding proteins (σ or ξ), which drive CBY1 nuclear export into a stable tripartite complex with β-catenin. The relative proximity of C22orf2 gene encoding for CBY1 to the BCR breakpoint on chromosome 22q11, whose translocation and rearrangement with the c-ABL is the causative event of chronic myeloid leukemia (CML), suggested that gene haploinsufficiency may play a role in the disease pathogenesis and progression...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29143175/vectors-for-expression-of-signal-peptide-dependent-proteins-in-baculovirus-insect-cell-systems-and-their-application-to-expression-and-purification-of-the-high-affinity-immunoglobulin-gamma-fc-receptor-i-in-complex-with-its-gamma-chain
#6
Le T M Le, Jens R Nyengaard, Monika M Golas, Bjoern Sander
Integral membrane proteins play a central role in various cellular functions and are important therapeutic targets. However, technical challenges in the overexpression and purification of membrane proteins often represent a limiting factor for biochemical and structural studies. Here, we constructed a set of vectors, derivatives of MultiBac vectors that can be used to express proteins with a cleavable N-terminal signal peptide in insect cells. We propose these vectors for expression of type I membrane proteins and other secretory pathway proteins that require the signal recognition particle for translocation to the endoplasmic reticulum (ER)...
November 15, 2017: Molecular Biotechnology
https://www.readbyqxmd.com/read/29137236/the-nucleocytoplasmic-translocation-and-up-regulation-of-ing5-protein-in-breast-cancer-a-potential-target-for-gene-therapy
#7
Xiao-Qing Ding, Shuang Zhao, Lei Yang, Xin Zhao, Gui-Feng Zhao, Shu-Peng Zhao, Zhi-Jie Li, Hua-Chuan Zheng
Here, we found that ING5 overexpression resulted in a lower proliferation, reduced glucose metabolism, S arrest, decreased migration and invasion, apoptotic induction, fat accumulation, autophagy, senescence and mesenchymal-epithelial-transition of breast cancer cells. It also suppressed the tumor growth of breast cancer cells by inhibiting proliferation, inducing apoptosis and autophagy. ING5-mediated chemoresistance was positively linked to Akt and NF-κB activation, MRP1 and GST-π overexpression, and FBXW7 hypoexpression...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29122814/non-endoplasmic-reticulum-based-calr-calreticulin-can-coordinate-heterocellular-calcium-signaling-and-vascular-function
#8
Lauren A Biwer, Miranda E Good, Kwangseok Hong, Rahul K Patel, Neha Agrawal, Robin Looft-Wilson, Swapnil K Sonkusare, Brant E Isakson
OBJECTIVE: In resistance arteries, endothelial cell (EC) extensions can make contact with smooth muscle cells, forming myoendothelial junction at holes in the internal elastic lamina (HIEL). At these HIEL, calcium signaling is tightly regulated. Because Calr (calreticulin) can buffer ≈50% of endoplasmic reticulum calcium and is expressed throughout IEL holes in small arteries, the only place where myoendothelial junctions form, we investigated the effect of EC-specific Calr deletion on calcium signaling and vascular function...
November 9, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29109429/knockdown-of-amyloid-precursor-protein-increases-calcium-levels-in-the-endoplasmic-reticulum
#9
Kinga Gazda, Jacek Kuznicki, Tomasz Wegierski
Familial Alzheimer's disease (AD) is caused by mutations in the genes that encode amyloid precursor protein (APP) and presenilins. Disturbances in calcium homeostasis have been observed in various cellular and animal models of AD and are proposed to underlie the pathogenesis of the disease. Furthermore, wildtype presenilins were shown to regulate endoplasmic reticulum (ER) calcium homeostasis, although their precise mechanism of action remains controversial. To investigate whether APP also affects ER calcium levels, we used RNA interference to target the APP gene in cultured T84 cells in combination with two types of ER calcium sensors...
November 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29104486/tanshinone-iia-inhibits-%C3%AE-catenin-nuclear-translocation-and-igf-2r-activation-via-estrogen-receptors-to-suppress-angiotensin-ii-induced-h9c2-cardiomyoblast-cell-apoptosis
#10
Ya-Fang Chen, Cecilia Hsuan Day, Nien-Hung Lee, Yu-Feng Chen, Jaw-Ji Yang, Chih-Hsueh Lin, Ray-Jade Chen, Peramaiyan Rajendran, Vijaya Padma Viswanadha, Chih-Yang Huang
Cardiomyopathy involves changes in the myocardial ultra-structure, hypertrophy, apoptosis, fibrosis and inflammation. Angiotensin II (AngII) stimulates the expression of insulin like-growth factors (IGF-2) and IGF-2 receptor (IGF-2R) in H9c2 cardiomyoblasts and subsequently leads to apoptosis. Estrogen receptors protect cardiomyocytes from apoptosis and fibrosis. Tanshinone IIA (TSN), a main active ingredient from Danshen, has been shown to protect cardiomyocytes from death caused by different stress signals...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/29089350/unspliced-xbp1-confers-vsmc-homeostasis-and-prevents-aortic-aneurysm-formation-via-foxo4-interaction
#11
Guizhen Zhao, Yi Fu, Zeyu Cai, Fang Yu, Ze Gong, Rongbo Dai, Yanhua Hu, Lingfang Zeng, Qingbo Xu, Wei Kong
Rationale: Although not fully understood, the phenotypic transition of vascular smooth muscle cells exhibits at the early onset of the pathology of aortic aneurysms. Exploring the key regulators that are responsible for maintaining the contractile phenotype of VSMCs may confer vascular homeostasis and prevent aneurysmal disease. X-box binding protein 1, which exists in a transcriptionally inactive unspliced form (XBP1u) and a spliced active form (XBP1s), is a key component in response to endoplasmic reticular (ER) stress...
October 31, 2017: Circulation Research
https://www.readbyqxmd.com/read/29075038/20-s-protopanaxadiol-enhances-angiogenesis-via-hif-1%C3%AE-mediated-vegf-secretion-by-activating-p70s6-kinase-and-benefits-wound-healing-in-genetically-diabetic-mice
#12
Er-Yun Zhang, Bo Gao, Hai-Lian Shi, Ling-Fang Huang, Li Yang, Xiao-Jun Wu, Zheng-Tao Wang
Impaired angiogenesis is one of the crucial factors that impede the wound healing process in diabetic foot ulcers (DFUs). In this study, we found that 20(S)-protopanaxadiol (PPD), an aglycone of ginsenosides in Panax notoginseng, stimulated angiogenesis and benefited wound healing in genetically diabetic mice. In HUVECs, PPD promoted cell proliferation, tube formation and VEGF secretion accompanied by increased nuclear translocalization of HIF-1α, which led to elevated VEGF mRNA expression. PPD activated both PI3K/Akt/mTOR and Raf/MEK/ERK signaling pathways in HUVECs, which were abrogated by LY294002 and PD98059...
October 27, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29054272/insights-on-the-hla-binding-peptidome-in-cancer
#13
Douglas F Lake
The intracellular compartments for proteolytic antigen processing in tumor cells produce peptides that are presented by MHC molecules to T cells. But first, the ubiquitin ligase system tags defective, misfolded, aged, and unstable proteins for degradation through the proteasome. Ubiqitinated proteins are unfolded and fed into the barrel-shaped core of the proteasome where a collection of multiple different proteases cleave proteins into oligopeptides. After exiting the proteasome, these oligopeptides are either completely degraded into amino acids or trimmed at the N- and C-termini so that they bind to transporter associated with antigen processing (TAP)...
2017: Enzymes
https://www.readbyqxmd.com/read/29045036/endoplasmic-reticulum-stress-regulates-oxygen-glucose-deprivation-induced-parthanatos-in-human-sh-sy5y-cells-via-improvement-of-intracellular-ros
#14
Hai-Feng Wang, Zong-Qi Wang, Ye Ding, Mei-Hua Piao, Chun-Sheng Feng, Guang-Fan Chi, Yi-Nan Luo, Peng-Fei Ge
AIMS: Endoplasmic reticulum (ER) stress has been demonstrated to regulate neuronal death caused by ischemic insults via activation of apoptosis, but it still remains unclear whether ER stress participates in regulation of parthanatos, a new type of programmed cell death characterized by PARP-1 overactivation and intracellular accumulation of PAR polymer. METHODS: we used oxygen-glucose deprivation (OGD) and human SH-SY5Y cells to simulate neuronal damage caused by ischemia...
October 16, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29042437/posttranslational-processing-and-membrane-translocation-of-the-yeast-regulatory-mid1-subunit-of-the-cch1-vgcc-nalcn-cation-channel-family
#15
Kazuko Iida, Jinfeng Teng, Toshihiko Cho, Sato Yoshikawa-Kimura, Hidetoshi Iida
Saccharomyces cerevisiae Mid1 is composed of 548 amino acids and a regulatory subunit of Cch1, a member of the eukaryotic pore-forming, four-domain cation channel family. The amino acid sequence and voltage insensitivity of Cch1 are more similar to those of Na+ leak channel non-selective (NALCN) than to the α1 subunit of voltage-gated Ca2+ channels (VGCCs). Despite a lack in overall primary sequence similarity, Mid1 resembles in some aspects VGCC α2/δ regulatory subunits and NALCN-associated proteins. Unlike animal α2/δ subunits, Mid1 and NALCN-associated proteins are essential for the function of the pore-forming subunit...
October 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29038295/characterization-of-aromatic-residue-controlled-protein-retention-in-the-endoplasmic-reticulum-of-saccharomyces-cerevisiae
#16
Meng Mei, Chao Zhai, Xinzhi Li, Yu Zhou, Wenfang Peng, Lixin Ma, Qinhong Wang, Brent L Iverson, Guimin Zhang, Li Yi
Endoplasmic reticulum (ER) retention sequence (ERS) is a characteristic short sequence that mediates protein retention in the ER of eukaryotic cells. However, little is known about the detailed molecular mechanism involved in ERS-mediated protein ER retention. Using a new surface display-based fluorescence technique that effectively quantifies ERS-promoted protein ER retention within Saccharomyces cerevisiae cells, we performed comprehensive ERS analyses. It was found that the length, type of amino acid residue, and additional residues at position -5 and -6 of C-terminal HDEL motif all determined the retention of ERS in the yeast ER...
October 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28981117/trehalose-ameliorates-oxidative-stress-mediated-mitochondrial-dysfunction-and-er-stress-via-selective-autophagy-stimulation-and-autophagic-flux-restoration-in-osteoarthritis-development
#17
Qian Tang, Gang Zheng, Zhenhua Feng, Yu Chen, Yiting Lou, Chenggui Wang, Xiaolei Zhang, Yu Zhang, Huazi Xu, Ping Shang, Haixiao Liu
Oxidative stress-related apoptosis and autophagy play crucial roles in the development of osteoarthritis (OA), a progressive cartilage degenerative disease with multifactorial etiologies. Here, we determined autophagic flux changes and apoptosis in human OA and tert-Butyl hydroperoxide (TBHP)-treated chondrocytes. In addition, we explored the potential protective effects of trehalose, a novel Mammalian Target of Rapamycin (mTOR)-independent autophagic inducer, in TBHP-treated mouse chondrocytes and a destabilized medial meniscus (DMM) mouse OA model...
October 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28978049/ros-independent-nrf2-activation-in-prostate-cancer
#18
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...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28978042/translocation-of-heme-oxygenase-1-contributes-to-imatinib-resistance-in-chronic-myelogenous-leukemia
#19
Bianca Schaefer, Soenke Behrends
Heme oxygenase-1 (HO-1) degrades heme to bilirubin. In addition, it is upregulated in malignant disease and has been described as an important factor for cancer prognosis and therapy. Under physiological conditions HO-1 is anchored to the endoplasmic reticulum (ER). Under stress conditions HO-1 can be cleaved and subsequently translocates to the cytosol and nucleus. In this study we systematically investigated the influence of HO-1's catabolic activity and subcellular localization on resistance against the tyrosine kinase inhibitor imatinib in leukemia cells by confocal laser scanning microscopy, hemoglobin synthesis experiments and cell viability assays...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28975041/escherichia-coli-o157-h7-suppresses-host-autophagy-and-promotes-epithelial-adhesion-via-tir-mediated-and-camp-independent-activation-of-protein-kinase-a
#20
Yansong Xue, Min Du, Haiqing Sheng, Carolyn J Hovde, Mei-Jun Zhu
Autophagy is a pivotal innate immune response that not only degrades cytosolic components, but also serves as one of the critical antimicrobial mechanisms eliminating intracellular pathogens. However, its role in host defense against extracellular pathogens is largely unknown. Here we showed that E. coli O157:H7 altered autophagy to evade host defense and facilitate adhesion. Enhancing host cell autophagy with tumor necrosis factor (TNF), host starvation or rapamycin reduced the adherence of E. coli O157:H7 to HT-29 cells...
2017: Cell Death Discovery
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