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https://www.readbyqxmd.com/read/28510570/bag-1-as-a-biomarker-in-early-breast-cancer-prognosis-a-systematic-review-with-meta-analyses
#1
E S Papadakis, T Reeves, N H Robson, T Maishman, G Packham, R I Cutress
BACKGROUND: The co-chaperone protein Bcl-2-associated athanogene-1 (BAG-1) is overexpressed in breast cancer and has been incorporated in the oncotype DX and PAM50 breast cancer prognostic assays. Bcl-2-associated athanogene-1 exists as multiple protein isoforms that interact with diverse partners, including chaperones Hsc70/Hsp70, Ser/Thr kinase Raf-1 and Bcl-2, to promote cancer cell survival. The BAG-1L isoform specifically binds to and increases the transcriptional activity of oestrogen receptor in cells, and in some, but not all studies, BAG-1 expression is predictive of clinical outcome in breast cancer...
May 16, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28509353/engineering-heat-tolerance-in-potato-by-temperature-dependent-expression-of-a-specific-allele-of-heat-shock-cognate-70
#2
Almudena Trapero-Mozos, Wayne L Morris, Laurence J M Ducreux, Karen McLean, Jennifer Stephens, Lesley Torrance, Glenn J Bryan, Robert D Hancock, Mark A Taylor
For many commercial potato cultivars, tuber yield is optimal at average day time temperatures in the range of 14-22⁰C. Further rises in ambient temperature can reduce or completely inhibit potato tuber production, with damaging consequences for both producer and consumer. The aim of this study was to use a genetic screen based on a model tuberisation assay to identify Quantitative Trait Loci (QTL) associated with enhanced tuber yield. A candidate gene encoding HSc70 was identified within one of the three QTL intervals associated with elevated yield in a Phureja-Tuberosum hybrid diploid potato population (06H1)...
May 16, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28484369/differential-targeting-of-hsp70-heat-shock-proteins-hspa6-and-hspa1a-with-components-of-a-protein-disaggregation-refolding-machine-in-differentiated-human-neuronal-cells-following-thermal-stress
#3
Catherine A S Deane, Ian R Brown
Heat shock proteins (Hsps) co-operate in multi-protein machines that counter protein misfolding and aggregation and involve DNAJ (Hsp40), HSPA (Hsp70), and HSPH (Hsp105α). The HSPA family is a multigene family composed of inducible and constitutively expressed members. Inducible HSPA6 (Hsp70B') is found in the human genome but not in the genomes of mouse and rat. To advance knowledge of this little studied HSPA member, the targeting of HSPA6 to stress-sensitive neuronal sites with components of a disaggregation/refolding machine was investigated following thermal stress...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28465257/5-fluorouracil-targets-histone-acetyltransferases-p300-cbp-in-the-treatment-of-colorectal-cancer
#4
Changzheng Du, Dandan Huang, Yifan Peng, Yunfeng Yao, Ying Zhao, Yang Yang, Haiying Wang, Linlin Cao, Wei-Guo Zhu, Jin Gu
Although 5-fluorouracil (5-FU) is known to interfere with the synthesis of ribonucleic acid and deoxyribonucleic acid, the mechanism underlying its therapeutic efficacy in colorectal cancer (CRC) has not been fully elucidated. We aimed to investigate the influence of 5-FU on histone acetylation, a well-established anti-cancer target, to reveal novel pharmacological effects of 5-FU and their significance for CRC therapy. Results demonstrated that 5-FU induces global histone de-acetylation in multiple CRC cell lines...
April 29, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28462495/cloning-and-expression-pattern-of-a-heat-shock-cognate-protein-70-gene-in-ticks-haemaphysalis-flava
#5
Lei Liu, Tian-Yin Cheng, Ya Yang
Ticks and tick-borne-diseases have serious public health implications, and screening feasible protein candidates for vaccines development is identified to be an effective alternative to control of tick infestations. In current study, we focused on cloning the full-length gene encoding a heat shock cognate protein 70 (Hsc70), a molecular chaperone of critical functional roles belonging to heat shock protein 70 (HSP70) family, in salivary glands of Haemaphysalis flava, namely Hf-Hsc70, and analyzing the expression of Hf-Hsc70 in different life phases, organs and ambient temperatures...
May 2, 2017: Parasitology Research
https://www.readbyqxmd.com/read/28442347/chronic-mitochondrial-calcium-elevation-suppresses-leaf-senescence
#6
Shijuan Fu, Luhua Li, Huimin Kang, Xue Yang, Shuzhen Men, Yuequan Shen
Mitochondria Ca(2+) overload has long been recognized as a cell death trigger. Unexpectedly, we demonstrated a signaling complex composed of Calmodulin (CaM), Arabidopsis thaliana Bcl-2-associated athanogene 5 (AtBAG5) and Heat-shock cognate 70 protein (Hsc70) within Arabidopsis thaliana mitochondria which transduces mitochondria Ca(2+) elevations to suppress leaf senescence. Gain- and loss-of-function AtBAG5 mutant plants revealed that, mitochondria Ca(2+) elevation significantly increase chlorophyll retention and decrease H2O2 level in dark-induced leaf senescence assay...
April 24, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28440485/sclareol-inhibits-cell-proliferation-and-sensitizes-cells-to-the-antiproliferative-effect-of-bortezomib-via-upregulating-the-tumor-suppressor-caveolin-1-in-cervical-cancer-cells
#7
Ting Zhang, Ting Wang, Peiling Cai
The anticancer effect of sclareol has long been reported, however, the exact mechanisms underlying the antitumorigenic effect of sclareol in cervical carcinoma remain to be fully elucidated. The present study analyzed cell proliferation and cell apoptosis by MTT and FITC‑Annexin V assays. The protein levels of caveolin‑1 (Cav‑1) and copper-zinc superoxide dismutase (SOD)1 were determined by western blotting, and the interaction of Cav1 and HSC70 was investigated by co‑immunoprecipitation experiments...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28428740/protein-quality-control-by-molecular-chaperones-in-neurodegeneration
#8
REVIEW
Aaron Ciechanover, Yong Tae Kwon
Protein homeostasis (proteostasis) requires the timely degradation of misfolded proteins and their aggregates by protein quality control (PQC), of which molecular chaperones are an essential component. Compared with other cell types, PQC in neurons is particularly challenging because they have a unique cellular structure with long extensions. Making it worse, neurons are postmitotic, i.e., cannot dilute toxic substances by division, and, thus, are highly sensitive to misfolded proteins, especially as they age...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28402954/chaperone-mediated-autophagy-compensates-for-impaired-macroautophagy-in-the-cirrhotic-liver-to-promote-hepatocellular-carcinoma
#9
Srinivas Chava, Christine Lee, Yucel Aydin, Partha K Chandra, Asha Dash, Milad Chedid, Swan N Thung, Krzysztof Moroz, Tong Wu, Nabeen C Nayak, Srikanta Dash
Macroautophagy and chaperone-mediated autophagy (CMA) represent two major lysosomal degradation processes and often compensate for one another to facilitate cell survival. The aim of this study was to determine whether these autophagy pathways could compensate for one another to promote HCC cell survival in the cirrhotic liver. Analysis of normal liver tissue showed no expression of glypican-3 or p62 proteins, suggesting that macroautophagy is the major contributor to autophagic flux under non-pathological conditions...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28396517/in-vitro-characterization-of-six-stub1-variants-in-spinocerebellar-ataxia-16-reveals-altered-structural-properties-for-the-encoded-chip-proteins
#10
Yasaman Pakdaman, Monica Sanchez-Guixé, Rune Kleppe, Sigrid Erdal, Helene J Bustad, Lise Bjørkhaug, Kristoffer Haugarvoll, Charalampos Tzoulis, Ketil Heimdal, Per M Knappskog, Stefan Johansson, Ingvild Aukrust
Spinocerebellar ataxia, autosomal recessive 16 (SCAR16) is caused by biallelic mutations in the STIP1 homology and U-box containing protein 1 (STUB1) gene encoding the ubiquitin E3 ligase and dimeric co-chaperone C-terminus of Hsc70-interacting protein (CHIP). It has been proposed that the disease mechanism is related to CHIP's impaired E3 ubiquitin ligase properties and/or interaction with its chaperones. However, there is limited knowledge on how these mutations affect the stability, folding, and protein structure of CHIP itself...
April 30, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28388579/rabies-viruses-leader-rna-interacts-with-host-hsc70-and-inhibits-virus-replication
#11
Ran Zhang, Chuangang Liu, Yunzi Cao, Muhammad Jamal, Xi Chen, Jinfang Zheng, Liang Li, Jing You, Qi Zhu, Shiyong Liu, Jinxia Dai, Min Cui, Zhen F Fu, Gang Cao
Viruses have been shown to be equipped with regulatory RNAs to evade host defense system. It has long been known that rabies virus (RABV) transcribes a small regulatory RNA, leader RNA (leRNA), which mediates the transition from viral RNA transcription to replication. However, the detailed molecular mechanism remains enigmatic. In the present study, we determined the genetic architecture of RABV leRNA and demonstrated its inhibitory effect on replication of wild-type rabies, DRV-AH08. The RNA immunoprecipitation results suggest that leRNA inhibits RABV replication via interfering the binding of RABV nucleoprotein with genomic RNA...
March 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28356524/sgta-dependent-regulation-of-hsc70-promotes-cytosol-entry-of-sv40-from-the-er
#12
Allison Dupzyk, Jeffrey M Williams, Parikshit Bagchi, Takamasa Inoue, Billy Tsai
Membrane penetration by non-enveloped viruses remains enigmatic. In the case of the non-enveloped polyomavirus SV40, the virus penetrates the endoplasmic reticulum (ER) membrane to reach the cytosol and then traffics to the nucleus to cause infection. We previously demonstrated that the cytosolic Hsc70-SGTA-Hsp105 complex is tethered to the ER membrane where Hsp105 and SGTA facilitate the extraction of SV40 into the cytosol. We now find that Hsc70 also ejects SV40 into the cytosol in a step regulated by SGTA...
March 29, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28346425/chip-stub1-regulates-the-warburg-effect-by-promoting-degradation-of-pkm2-in-ovarian-carcinoma
#13
Y Shang, J He, Y Wang, Q Feng, Y Zhang, J Guo, J Li, S Li, Y Wang, G Yan, F Ren, Y Shi, J Xu, N Zeps, Y Zhai, D He, Z Chang
Tumor cells preferentially adopt aerobic glycolysis for their energy supply, a phenomenon known as the Warburg effect. It remains a matter of debate as to how the Warburg effect is regulated during tumor progression. Here, we show that CHIP (carboxyl terminus of Hsc70-interacting protein), a U-box E3 ligase, suppresses tumor progression in ovarian carcinomas by inhibiting aerobic glycolysis. While CHIP is downregulated in ovarian carcinoma, induced expression of CHIP results in significant inhibition of the tumor growth examined by in vitro and in vivo experiments...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28341812/parkinson-s-disease-associated-receptor-gpr37-is-an-er-chaperone-for-lrp6
#14
Birgit S Berger, Sergio P Acebron, Jessica Herbst, Stefan Koch, Christof Niehrs
Wnt/β-catenin signaling plays a key role in embryonic development, stem cell biology, and neurogenesis. However, the mechanisms of Wnt signal transmission, notably how the receptors are regulated, remain incompletely understood. Here we describe that the Parkinson's disease-associated receptor GPR37 functions in the maturation of the N-terminal bulky β-propellers of the Wnt co-receptor LRP6. GPR37 is required for Wnt/β-catenin signaling and protects LRP6 from ER-associated degradation via CHIP (carboxyl terminus of Hsc70-interacting protein) and the ATPase VCP GPR37 is highly expressed in neural progenitor cells (NPCs) where it is required for Wnt-dependent neurogenesis...
May 2017: EMBO Reports
https://www.readbyqxmd.com/read/28339481/proteomic-analysis-of-injured-storage-roots-in-cassava-manihot-esculenta-crantz-under-postharvest-physiological-deterioration
#15
Yuling Qin, Astride Stéphanie Mouafi Djabou, Feifei An, Kaimian Li, Zhaogui Li, Long Yang, Xiaojing Wang, Songbi Chen
Postharvest physiological deterioration (PPD) is a global challenge in the improvement of cassava value chain. However, how to reduce cassava spoilage and reveal the mechanism of injured cassava storage roots in response to PPD were poorly understood. In the present study, we investigated the activities of antioxidant enzymes of cassava injured storage roots in PPD-susceptible (SC9) and PPD-tolerant (QZ1) genotypes at the time-points from 0h to 120h, and further analyzed their proteomic changes using two-dimensional electrophoresis (2-DE) in combination with MALDI-TOF-MS/MS...
2017: PloS One
https://www.readbyqxmd.com/read/28338815/enhanced-tenogenic-differentiation-and-tendon-like-tissue-formation-by-chip-overexpression-in-tendon-derived-stem-cells
#16
Weifeng Han, Lei Chen, Junpeng Liu, Ai Guo
The carboxyl terminus of Hsc70-interacting protein (CHIP, also known as STUB1) plays critical roles in the proliferation and differentiation of many types of cells. The potential function of CHIP in tendon-derived stem cells (TDSCs) remains largely unknown at present. Here, we investigated the effects of CHIP on tenogenic differentiation of TDSCs via lentivirus-mediated overexpression. Forced expression of CHIP induced morphological changes and significantly enhanced cell proliferation, as well as tendon differentiation in vitro...
February 22, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28323023/internalization-axonal-transport-and-release-of-fibrillar-forms-of-alpha-synuclein
#17
Gregor Bieri, Aaron D Gitler, Michel Brahic
Intra-neuronal protein aggregates made of fibrillar alpha-synuclein (α-syn) are the hallmark of Parkinson's disease (PD). With time, these aggregates spread through the brain following axonal projections. Understanding the mechanism of this spread is central to the study of the progressive nature of PD. Here we review data relevant to the uptake, transport and release of α-syn fibrils. We summarize several cell surface receptors that regulate the uptake of α-syn fibrils by neurons. The aggregates are then transported along axons, both in the anterograde and retrograde direction...
March 16, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28320779/the-g2385r-risk-factor-for-parkinson-s-disease-enhances-chip-dependent-intracellular-degradation-of-lrrk2
#18
Iakov N Rudenko, Alice Kaganovich, Rebekah G Langston, Aleksandra Beilina, Kelechi Ndukwe, Ravindran Kumaran, Allissa A Dillman, Ruth Chia, Mark R Cookson
Autosomal dominant mutations in leucine-rich repeat kinase 2 ( LRRK2 ) are associated with Parkinson's disease (PD). Most pathogenic LRRK2 mutations result in amino-acid substitutions in the central ROC-COR-Kinase triple domain and affect enzymatic functions of the protein. However, there are several variants in LRRK2 , including the risk factor G2385R, that impact PD pathogenesis by unknown mechanisms. Previously, we have shown that G2385R LRRK2 has decreased kinase activity in vitro and altered affinity to LRRK2 interactors...
March 20, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28238968/changes-in-macroautophagy-chaperone-mediated-autophagy-and-mitochondrial-metabolism-in-murine-skeletal-and-cardiac-muscle-during-aging
#19
Jin Zhou, Shu Yun Chong, Andrea Lim, Brijesh K Singh, Rohit A Sinha, Adam B Salmon, Paul M Yen
Aging causes a general decline in cellular metabolic activity, and function in different tissues and whole body homeostasis. However, the understanding about the metabolomic and autophagy changes in skeletal muscle and heart during aging is still limited. We thus examined markers for macroautophagy, chaperone-mediated autophagy (CMA), mitochondrial quality control, as well as cellular metabolites in skeletal and cardiac muscle from young (5 months old) and aged (27 months old) mice. We found decreased autophagic degradation of p62 and increased ubiquitinated proteins in both tissues from aged mice, suggesting a decline in macroautophagy during aging...
February 26, 2017: Aging
https://www.readbyqxmd.com/read/28220454/the-remarkable-multivalency-of-the-hsp70-chaperones
#20
REVIEW
Erik R P Zuiderweg, Lawrence E Hightower, Jason E Gestwicki
Hsp70 proteins are key to maintaining intracellular protein homeostasis. To carry out this task, they employ a large number of cochaperones and adapter proteins. Here, we review what is known about the interaction between the chaperones and partners, with a strong slant toward structural biology. Hsp70s in general, and Hsc70 (HSPA8) in particular, display an amazing array of interfaces with their protein cofactors. We also review the known interactions between Hsp70s with lipids and with active compounds that may become leads toward Hsp70 modulation for treatment of a variety of diseases...
March 2017: Cell Stress & Chaperones
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