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https://www.readbyqxmd.com/read/29769335/bag2-is-a-component-of-a-cytosolic-extraction-machinery-that-promotes-membrane-penetration-of-a-nonenveloped-virus
#1
Allison Dupzyk, Billy Tsai
During entry, the nonenveloped polyomavirus (PyV) SV40 traffics from the cell surface to the endoplasmic reticulum (ER) where it penetrates the ER membrane to reach the cytosol; the virus then transports into the nucleus to cause infection. Although a coherent understanding of SV40's host entry is emerging, how the virus is ejected from the ER into the cytosol remains mysterious. Our previous analyses revealed that the cytosolic Hsc70-SGTA-Hsp105 complex binds to and extracts SV40 from the ER into the cytosol...
May 16, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29765493/long-term-exercise-protects-against-cellular-stresses-in-aged-mice
#2
Irina Belaya, Masataka Suwa, Tao Chen, Rashid Giniatullin, Katja M Kanninen, Mustafa Atalay, Shuzo Kumagai
The current study examined the effect of aging and long-term wheel-running on the expression of heat shock protein (HSP), redox regulation, and endoplasmic reticulum (ER) stress markers in tibialis anterior (T.A.) and soleus muscle of mice. Male mice were divided into young (Y, 3-month-old), old-sedentary (OS, 24-month-old), and old-exercise (OE, 24-month-old) groups. The OE group started voluntary wheel-running at 3 months and continued until 24 months of age. Aging was associated with a higher thioredoxin-interacting protein (TxNiP) level, lower thioredoxin-1 (TRX-1) to TxNiP ratio-a determinant of redox regulation and increased CHOP, an indicator of ER stress-related apoptosis signaling in both muscles...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29764935/the-disorderly-conduct-of-hsc70-and-its-interaction-with-the-alzheimer-s-related-tau-protein
#3
Isabelle R Taylor, Atta Ahmad, Taia Wu, Bryce A Nordhues, Anup Bhullar, Jason E Gestwicki, Erik R P Zuiderweg
Hsp70 chaperones bind to various protein substrates for folding, trafficking, and degradation. Considerable structural information is available about how prokaryotic Hsp70 (DnaK) binds substrates, but less is known about mammalian Hsp70s, of which there are 13 isoforms encoded in the human genome. Here, we report the interaction between the human Hsp70 isoform heat shock cognate 71 KDa protein (Hsc70 or HSPA8) and peptides derived from the microtubule-associated protein tau, which is linked to Alzheimer's disease...
May 15, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29738468/-cawrky40b-in-pepper-acts-as-a-negative-regulator-in-response-to-ralstonia-solanacearum-by-directly-modulating-defense-genes-including-cawrky40
#4
Muhammad Ifnan Khan, Yangwen Zhang, Zhiqin Liu, Jiong Hu, Cailing Liu, Sheng Yang, Ansar Hussain, Muhammad Furqan Ashraf, Ali Noman, Lei Shen, Xiaoqin Xia, Feng Yang, Deyi Guan, Shuilin He
WRKY transcription factors (TFs) have been implicated in plant growth, development, and in response to environmental cues; however, the function of the majority of pepper WRKY TFs remains unclear. In the present study, we functionally characterized CaWRKY40b , a homolog of AtWRKY40 , in pepper immunity. Ralstonia solanacearum inoculation (RSI) in pepper plants resulted in downregulation of CaWRKY40b transcript, and green fluorescent protein (GFP)-tagged CaWRKY40b was localized to the nuclei when transiently overexpressed in the leaves of Nicotiana benthamiana ...
May 8, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29695419/hepatitis-c-virus-ns5a-protein-promotes-the-lysosomal-degradation-of-hepatocyte-nuclear-factor-1%C3%AE-via-chaperone-mediated-autophagy
#5
Chieko Matsui, Lin Deng, Nanae Minami, Takayuki Abe, Kazuhiko Koike, Ikuo Shoji
Hepatitis C virus (HCV) infection is closely associated with type 2 diabetes. We reported that HCV infection induces the lysosomal degradation of hepatocyte nuclear factor 1alpha (HNF-1α) via interaction with HCV NS5A protein, thereby suppressing GLUT2 gene expression. Molecular mechanisms of selective degradation of HNF-1α caused by NS5A are largely unknown. Chaperone-mediated autophagy (CMA) is a selective lysosomal degradation pathway. Here, we investigated whether CMA is involved in the selective degradation of HNF-1α in HCV-infected cells and observed that the pentapeptide spanning from aa 130 to aa 134 of HNF-1α matches the rule for the CMA-targeting motif, also known as KFERQ motif...
April 25, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29686306/anisomycin-prevents-ogd-induced-necroptosis-by-regulating-the-e3-ligase-chip
#6
Mi-Bo Tang, Yu-Sheng Li, Shao-Hua Li, Yuan Cheng, Shuo Zhang, Hai-Yang Luo, Cheng-Yuan Mao, Zheng-Wei Hu, Jonathan C Schisler, Chang-He Shi, Yu-Ming Xu
Necroptosis is an essential pathophysiological process in cerebral ischemia-related diseases. Therefore, targeting necroptosis may prevent cell death and provide a much-needed therapy. Ansiomycin is an inhibitor of protein synthesis which can also activate c-Jun N-terminal kinases. The present study demonstrated that anisomycin attenuated necroptosis by upregulating CHIP (carboxyl terminus of Hsc70-interacting protein) leading to the reduced levels of receptor-interacting protein kinase 1 (RIPK1) and receptor-interacting protein kinase 3 (RIPK3) proteins in two in vitro models of cerebral ischemia...
April 23, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29665004/thiostrepton-degrades-mutant-p53-by-eliciting-an-autophagic-response-in-sw480-cells
#7
Dhanya Kalathil, Manu Prasad, Maharrish Chelladurai, Samu John, Asha S Nair
Mutations in p53 gene are one of the hallmarks of tumor development. Specific targeting of mutant p53 protein has a promising role in cancer therapeutics. Our preliminary observation showed destabilization of mutant p53 protein in SW480, MiaPaCa and MDAMB231 cell lines upon thiostrepton treatment. In order to elucidate the mechanism of thiostrepton triggered mutant p53 degradation, we explored the impact of proteasome inhibition on activation of autophagy. Combined treatment of thiostrepton and cycloheximide/chloroquine prevented the degradation of mutant p53 protein, reinforcing autophagy as the means of mutant p53 destabilization...
April 17, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29662435/ac2-26-induces-ikk%C3%AE-degradation-through-chaperone-mediated-autophagy-via-hspb1-in-ncm-treated-microglia
#8
Lu Liu, Dandan An, Junying Xu, Bin Shao, Xing Li, Jing Shi
Annexin A1 (ANXA1) is an endogenous protein with potent anti-inflammatory properties in the brain. Although ANXA1 has been predominantly studied for its binding to formyl peptide receptors (FPRs) on plasma membranes, little is known regarding whether this protein has an anti-inflammatory effect in the cytosol. Here, we investigated the mechanism by which the ANXA1 peptide Ac2-26 decreases high TNF-α production and IKKβ activity, which was caused by oxygen glucose deprivation/reperfusion (OGD/R)-induced neuronal conditioned medium (NCM) in microglia...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29587857/hsp70-from-the-antarctic-sea-urchin-sterechinus-neumayeri-molecular-characterization-and-expression-in-response-to-heat-stress
#9
Marcelo González-Aravena, Camila Calfio, Luis Mercado, Byron Morales-Lange, Jorn Bethke, Julien De Lorgeril, César A Cárdenas
BACKGROUND: Heat stress proteins are implicated in stabilizing and refolding denatured proteins in vertebrates and invertebrates. Members of the Hsp70 gene family comprise the cognate heat shock protein (Hsc70) and inducible heat shock protein (Hsp70). However, the cDNA sequence and the expression of Hsp70 in the Antarctic sea urchin are unknown. METHODS: We amplified and cloned a transcript sequence of 1991 bp from the Antarctic sea urchin Sterechinus neumayeri, experimentally exposed to heat stress (5  and 10 °C for 1, 24 and 48 h)...
March 27, 2018: Biological Research
https://www.readbyqxmd.com/read/29571733/the-guanine-nucleotide-binding-protein-%C3%AE-subunit-protein-chgnaq-positively-regulates-hsc70-transcription-in-crassostrea-hongkongensis
#10
Lingli Zhang, Delin Xu, Miao Cui, Lei Tang, Tinglong Hou, Qizhong Zhang
Gnaq, one of Guanine nucleotide-binding protein α subunits, was isolated from cellular nucleus extracts of oyster Crassostrea hongkongensis gills with biotin-labeled ChHsc70 promoter by means of DNA-affinity purification, and preliminarily identified with mass spectrometry analysis. ChGnaq mRNA depletion by RNAi technique led to clear reduction in ChHsc70 mRNA expression of C. hongkongensis hemocytes. Correspondently, ChGnaq over-expression in heterologous HEK293T cells correlated with elevated expression activation of ChHsc70 promoter...
March 20, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29540800/hsc70-2-is-required-for-beet-black-scorch-virus-infection-through-interaction-with-replication-and-capsid-proteins
#11
Xiaoling Wang, Xiuling Cao, Min Liu, Ruiqi Zhang, Xin Zhang, Zongyu Gao, Xiaofei Zhao, Kai Xu, Dawei Li, Yongliang Zhang
Dissecting the complex molecular interplay between the host plant and invading virus improves our understanding of the mechanisms underlying viral pathogenesis. In this study, immunoprecipitation together with the mass spectrometry analysis revealed that the heat shock protein 70 (Hsp70) family homolog, Hsc70-2, was co-purified with beet black scorch virus (BBSV) replication protein p23 and coat protein (CP), respectively. Further experiments demonstrated that Hsc70-2 interacts directly with both p23 and CP, whereas there is no interaction between p23 and CP...
March 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29531792/dnajc5-facilitates-usp19-dependent-unconventional-secretion-of-misfolded-cytosolic-proteins
#12
Yue Xu, Lei Cui, Anthony Dibello, Lihui Wang, Juhyung Lee, Layla Saidi, Jin-Gu Lee, Yihong Ye
Cell-to-cell transmission of misfolded proteins propagates proteotoxic stress in multicellular organisms when transmitted polypeptides serve as a seeding template to cause protein misfolding in recipient cells, but how misfolded proteins are released from cells to initiate this process is unclear. Misfolding-associated protein secretion (MAPS) is an unconventional protein-disposing mechanism that specifically exports misfolded cytosolic proteins including various neurodegenerative disease-causing proteins. Here we establish the HSC70 co-chaperone DNAJC5 as an essential mediator of MAPS...
2018: Cell Discovery
https://www.readbyqxmd.com/read/29510992/loss-of-the-nuclear-pool-of-ubiquitin-ligase-chip-stub1-in-breast-cancer-unleashes-the-mzf1-cathepsin-pro-oncogenic-program
#13
Haitao Luan, Bhopal Mohapatra, Timothy A Bielecki, Insha Mushtaq, Sameer Mirza, Tameka A Jennings, Robert J Clubb, Wei An, Dena Ahmed, Rokaya El-Ansari, Matthew D Storck, Nitish K Mishra, Chittibabu Guda, Yuri M Sheinin, Jane L Meza, Srikumar Raja, Emad A Rakha, Vimla Band, Hamid Band
CHIP/STUB1 ubiquitin ligase is a negative co-chaperone for HSP90/HSC70, and its expression is reduced or lost in several cancers, including breast cancer. Using an extensive and well-annotated breast cancer tissue collection, we identified the loss of nuclear but not cytoplasmic CHIP to predict more aggressive tumorigenesis and shorter patient survival, with loss of CHIP in two thirds of ErbB2+ and triple-negative breast cancers (TNBC) and in one third of ER+ breast cancers. Reduced CHIP expression was seen in breast cancer patient-derived xenograft tumors and in ErbB2+ and TNBC cell lines...
May 15, 2018: Cancer Research
https://www.readbyqxmd.com/read/29503157/chaperone-independent-peripheral-quality-control-of-cftr-by-rffl-e3-ligase
#14
Tsukasa Okiyoneda, Guido Veit, Ryohei Sakai, Misaki Aki, Takeshi Fujihara, Momoko Higashi, Seiko Susuki-Miyata, Masanori Miyata, Norihito Fukuda, Akihiko Yoshida, Haijin Xu, Pirjo M Apaja, Gergely L Lukacs
The peripheral protein quality control (QC) system removes non-native membrane proteins, including ΔF508-CFTR, the most common CFTR mutant in cystic fibrosis (CF), from the plasma membrane (PM) for lysosomal degradation by ubiquitination. It remains unclear how unfolded membrane proteins are recognized and targeted for ubiquitination and how they are removed from the apical PM. Using comprehensive siRNA screens, we identified RFFL, an E3 ubiquitin (Ub) ligase that directly and selectively recognizes unfolded ΔF508-CFTR through its disordered regions...
March 26, 2018: Developmental Cell
https://www.readbyqxmd.com/read/29491214/bisphenol-a-and-its-derivatives-induce-degradation-of-hif-1alpha-via-the-lysosomal-pathway-in-human-hepatocarcinoma-cell-line-hep3b
#15
Yukino Kobayashi, Ami Oguro, Susumu Imaoka
Bisphenol A (BPA, 2,2-bis(4-hydroxyphenyl)propane), one of the phenolic compounds widely used in the manufacture of plastic and epoxy resins, is known as an endocrine disruptor. In a previous study, we found that BPA induced hypoxia inducible factor-1alpha (HIF-1alpha) degradation by dissociation from heat shock protein 90 (Hsp90). In this study, to investigate the structural requirements for degradation of HIF-1alpha, we estimated the effect of BPA derivatives (BPE, BPF, BPB, Dimethyl butylidene diphenol (DMBDP), Ethyl hexylidene diphenol (EHDP), Bishydroxyphenyl cyclohexane (BHCH), and Methyl benzylidene bisphenol (MBBP)) on HIF-1alpha protein degradation, using human hepatocarcinoma cell line, Hep3B...
2018: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29398086/autolysin-mediated-adherence-of-staphylococcus-aureus-with-fibronectin-gelatin-and-heparin
#16
Chandni Porayath, Maneesha K Suresh, Raja Biswas, Bipin G Nair, Nandita Mishra, Sanjay Pal
Major autolysin (Atl) of Staphylococcus aureusis a cell surface associated peptidoglycan hydrolase with amidase and glucosaminidase domains. Atl enzymes (amidase and glucosaminidase) are known to participate in biofilm formation and also can bind with host matrices. Earlier studies demonstrated the binding of Atlwithfibronectin, thrombospondin 1, vitronectin and heat shock cognate protein Hsc70. Here, we have shown, Atl mediates attachment of S.aureus to heparin and gelatine as well. The atl mutant strain demonstrated around 2...
April 15, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29370405/oviductal-extracellular-vesicles-oviductosomes-ovs-are-conserved-in-humans-murine-ovs-play-a-pivotal-role-in-sperm-capacitation-and-fertility
#17
Pradeepthi Bathala, Zeinab Fereshteh, Kun Li, Amal A Al-Dossary, Deni S Galileo, Patricia A Martin-DeLeon
STUDY QUESTIONS: Are extracellular vesicles (EVs) in the murine oviduct (oviductosomes, OVS) conserved in humans and do they play a role in the fertility of Pmca4-/- females? SUMMARY ANSWER: OVS and their fertility-modulating proteins are conserved in humans, arise via the apocrine pathway, and mediate a compensatory upregulation of PMCA1 (plasma membrane Ca2+-ATPase 1) in Pmca4-/- female mice during proestrus/estrus, to account for their fertility. WHAT IS KNOWN ALREADY: Recently murine OVS were identified and shown during proestrus/estrus to express elevated levels of PMCA4 which they can deliver to sperm...
March 1, 2018: Molecular Human Reproduction
https://www.readbyqxmd.com/read/29326975/identifying-the-substrate-proteins-of-u-box-e3s-e4b-and-chip-by-orthogonal-ubiquitin-transfer
#18
Karan Bhuripanyo, Yiyang Wang, Xianpeng Liu, Li Zhou, Ruochuan Liu, Duc Duong, Bo Zhao, Yingtao Bi, Han Zhou, Geng Chen, Nicholas T Seyfried, Walter J Chazin, Hiroaki Kiyokawa, Jun Yin
E3 ubiquitin (UB) ligases E4B and carboxyl terminus of Hsc70-interacting protein (CHIP) use a common U-box motif to transfer UB from E1 and E2 enzymes to their substrate proteins and regulate diverse cellular processes. To profile their ubiquitination targets in the cell, we used phage display to engineer E2-E4B and E2-CHIP pairs that were free of cross-reactivity with the native UB transfer cascades. We then used the engineered E2-E3 pairs to construct "orthogonal UB transfer (OUT)" cascades so that a mutant UB (xUB) could be exclusively used by the engineered E4B or CHIP to label their substrate proteins...
January 2018: Science Advances
https://www.readbyqxmd.com/read/29317501/most-mutations-that-cause-spinocerebellar-ataxia-autosomal-recessive-type-16-scar16-destabilize-the-protein-quality-control-e3-ligase-chip
#19
Adam J Kanack, Oliver J Newsom, Kenneth Matthew Scaglione
The accumulation of misfolded proteins promotes protein aggregation and neuronal death in many neurodegenerative diseases. To counteract misfolded protein accumulation, neurons have pathways that recognize and refold or degrade aggregation-prone proteins. One U-box-containing E3 ligase, C terminus of Hsc70-interacting protein (CHIP), plays a key role in this process, targeting misfolded proteins for proteasomal degradation. CHIP plays a protective role in mouse models of neurodegenerative disease, and in humans, mutations in CHIP cause spinocerebellar ataxia autosomal recessive type 16 (SCAR16), a fatal neurodegenerative disease characterized by truncal and limb ataxia that results in gait instability...
February 23, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29317151/structure-activity-relationships-of-cryptopleurine-analogs-with-e-ring-modifications-as-anti-hepatitis-c-virus-agents
#20
Ying Wang, Shao-Ru Chen, Xiaoming Yang, Kuo-Hsiung Lee, Yung-Chi Cheng
The tylophorine analog rac-cryptopleurine exhibited potent anti-hepatitis C virus (HCV) activity through allosteric regulation of ATPase activity of heat shock cognate protein 70 (Hsc70). We evaluated the impact of modifications on the E-ring of rac-cryptopleurine to the inhibitory activity against HCV replication and regulation of ATPase activity of Hsc70. Cryptopleurine analog YXM-110 with a 13α-hydroxyl group maintained activity against HCV and promoted ATP/ADP turnover of Hsc70; however, compounds with hydroxyl groups at other positions or with other orientations (YXM-109, YXM-139, and YXM-140) did not exhibit similar activities...
February 1, 2018: Bioorganic & Medicinal Chemistry
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