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https://www.readbyqxmd.com/read/29326975/identifying-the-substrate-proteins-of-u-box-e3s-e4b-and-chip-by-orthogonal-ubiquitin-transfer
#1
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
#2
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 result in gait instability...
January 9, 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
#3
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...
December 20, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29300467/disrupted-hydrogen-bond-network-and-impaired-atpase-activity-in-an-hsc70-cysteine-mutant
#4
John P O'Donnell, Heather M Marsh, Holger Sondermann, Carolyn Sevier
The ATPase domain of the 70-kD heat shock protein (Hsp70) family members shows a high degree of sequence, structural, and functional homology across species. A broadly conserved residue within the Hsp70 ATPase domain that captured our attention is an unpaired cysteine, positioned proximal to the site of nucleotide binding. Prior studies of several Hsp70 family members show this cysteine is not required for Hsp70 ATPase activity, yet select amino acid replacements of the cysteine can dramatically alter ATP hydrolysis...
January 4, 2018: Biochemistry
https://www.readbyqxmd.com/read/29298892/hspb1-and-hsc70-chaperones-engage-distinct-tau-species-and-have-different-inhibitory-effects-on-amyloid-formation
#5
Hannah E R Baughman, Amanda F Clouser, Rachel E Klevit, Abhinav Nath
The microtubule-associated protein tau forms insoluble, amyloid-type aggregates in various dementias, most notably Alzheimer's disease. Cellular chaperone proteins play important roles in maintaining protein solubility and preventing aggregation in the crowded cellular environment. While tau is known to interact with numerous chaperones, it remains unclear how these chaperones function mechanistically to prevent tau aggregation and how chaperones from different classes compare in terms of mechanism. Here, we focused on the small heat shock protein HspB1 and the constitutive chaperone Hsc70 (also known as HspA8), and report how each chaperone interacts with tau to prevent its fibril formation...
January 3, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29277610/the-transcriptional-factor-yb-1-positively-regulates-hsc70-transcription-in-crassostrea-hongkongensis
#6
Huiru Liu, Delin Xu, Miao Cui, Tinglong Hou, Qizhong Zhang
A Y-box binding protein ChYB-1 was discovered as a ChHsc70 promoter-associated protein in Crassostrea hongkongensis by DNA-affinity purification and mass spectrometry analysis. The overexpression of ChYB-1 in heterologous HEK293T cells led to clear enhancement of ChHsc70 promoter expression, while ChYB-1 depletion correlated with significant reduction of ChHsc70 transcription in the hemocytes of C. hongkongensis. Quantitative Real-time PCR analysis revealed that both ChHsc70 and ChYB-1 were transcriptionally responsive to external chemical or physical stressors...
December 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29277604/tolerance-to-hypometabolism-and-arousal-induced-by-hibernation-in-the-apple-snail-pomacea-canaliculata-caenogastropoda-ampullariidae
#7
Maximiliano Giraud-Billoud, Alfredo Castro-Vazquez, Alejandra D Campoy-Diaz, Pablo M Giuffrida, Israel A Vega
Pomacea canaliculata may serve as a model organism for comparative studies of oxidative damage and antioxidant defenses in active, hibernating and arousing snails. Oxidative damage (as TBARS), free radical scavenging capacity (as ABTS+ oxidation), uric acid (UA) and glutathione (GSH) concentrations, activities of superoxide dismutase (SOD) and catalase (CAT), and the protein expression levels of heat shock proteins (Hsp70, Hsc70, Hsp90) were studied in digestive gland, kidney and foot. Tissue TBARS of hibernating snails (45days) was higher than active snails...
December 19, 2017: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/29275183/endocrine-disruptors-in-soil-effects-of-bisphenol-a-on-gene-expression-of-the-earthworm-eisenia-fetida
#8
M Novo, I Verdú, D Trigo, J L Martínez-Guitarte
Xenobiotics such as bisphenol A (BPA), are present in biosolids, which are applied as organic fertilizers in agricultural fields. Their effects on soil life have been poorly assessed, and this is particularly important in the case of earthworms, which represent the main animal biomass in this medium. In the present work we study the impacts of BPA on gene expression of Eisenia fetida, a widely used ecotoxicological model. Chronic soil tests and acute contact tests were performed, and gene expression was analyzed in total tissue and in masculine reproductive organs of the earthworms...
December 21, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/29273565/identification-of-d-amino-acid-oxidase-and-propiverine-interaction-partners-and-their-potential-role-in-the-propiverine-mediated-nephropathy
#9
Marcia Y Maier, Lisanne Luks, Oliver Baudendistel, Valentin Wittmann, Daniel R Dietrich
Propiverine, a frequently-prescribed pharmaceutical for the treatment of symptoms associated with overactive bladder syndrome, provoked massive intranuclear and cytosolic protein inclusions in rat proximal tubule epithelium, primarily consisting of the peroxisomal targeting signal 1 (PTS1) containing protein d-amino acid oxidase (DAAO). As this type of nephropathy was also observed for other drugs, the aim was to determine whether propiverine interferes with trafficking and/or import of peroxisomal proteins...
December 19, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29247007/chaperone-mediated-autophagy-and-endosomal-microautophagy-joint-by-a-chaperone
#10
Kumsal A Tekirdag, Ana Maria Cuervo
A variety of mechanisms deliver cytosolic materials to the lysosomal compartment for degradation through autophagy. Here, we focus on two autophagic pathways, chaperone-mediated autophagy and endosomal microautophagy that rely on the cytosolic chaperone hsc70 for substrate targeting. Although hsc70 participates in triage of proteins for degradation by different proteolytic systems, the common characteristic shared by these two forms of autophagy, is that hsc70 binds directly to a specific five amino acids motif in the cargo protein for its autophagic targeting...
December 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29242247/chip-regulates-aquaporin-2-quality-control-and-body-water-homeostasis
#11
Qi Wu, Hanne B Moeller, Donté A Stevens, Rebekah Sanchez-Hodge, Gabrielle Childers, Marleen L A Kortenoeven, Lei Cheng, Lena L Rosenbaek, Carrie Rubel, Cam Patterson, Trairak Pisitkun, Jonathan C Schisler, Robert A Fenton
The importance of the kidney distal convoluted tubule (DCT) and cortical collecting duct (CCD) is highlighted by various water and electrolyte disorders that arise when the unique transport properties of these segments are disturbed. Despite this critical role, little is known about which proteins have a regulatory role in these cells and how these cells can be regulated by individual physiologic stimuli. By combining proteomics, bioinformatics, and cell biology approaches, we found that the E3 ubiquitin ligase CHIP is highly expressed throughout the collecting duct; is modulated in abundance by vasopressin; interacts with aquaporin-2 (AQP2), Hsp70, and Hsc70; and can directly ubiquitylate the water channel AQP2 in vitro shRNA knockdown of CHIP in CCD cells increased AQP2 protein t1/2 and reduced AQP2 ubiquitylation, resulting in greater levels of AQP2 and phosphorylated AQP2...
December 14, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29218503/differential-alterations-in-metabolism-and-proteolysis-related-proteins-in-human-parkinson-s-disease-substantia-nigra
#12
Edna Grünblatt, Josefine Ruder, Camelia Maria Monoranu, Peter Riederer, Moussa Bh Youdim, Silvia A Mandel
Parkinson's disease is the most common neurodegenerative disorder after Alzheimer's disease, with the majority of cases being sporadic or "idiopathic". The aetiology of the sporadic form is still unknown, but there is a broad consensus that Parkinson's disease involves multiple pathways. In previous human post-mortem studies investigating substantia nigra of parkinsonian subjects, gene expression alterations in various metabolic pathways including protein folding, trafficking, aggregation, ubiquitination and oxidative stress were found...
December 7, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29212816/complete-suppression-of-htt-fibrilization-and-disaggregation-of-htt-fibrils-by-a-trimeric-chaperone-complex
#13
Annika Scior, Alexander Buntru, Kristin Arnsburg, Anne Ast, Manuel Iburg, Katrin Juenemann, Maria Lucia Pigazzini, Barbara Mlody, Dmytro Puchkov, Josef Priller, Erich E Wanker, Alessandro Prigione, Janine Kirstein
Huntington's disease (HD) is a neurodegenerative disorder caused by an expanded CAG trinucleotide repeat in the huntingtin gene (HTT). Molecular chaperones have been implicated in suppressing or delaying the aggregation of mutant Htt. Using in vitro and in vivo assays, we have identified a trimeric chaperone complex (Hsc70, Hsp110, and J-protein) that completely suppresses fibrilization of HttExon1Q48 The composition of this chaperone complex is variable as recruitment of different chaperone family members forms distinct functional complexes...
December 6, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29180285/hsc70-regulates-the-ires-activity-and-serves-as-an-antiviral-target-of-enterovirus-a71-infection
#14
Qi Dong, Rutin Men, Xuelian Dan, Ying Chen, Huangcan Li, Gong Chen, Benny Zee, Maggie H T Wong, Ming-Liang He
Enterovirus A71 (EV-A71) is a small positive-stranded RNA virus that causes human hand, foot and mouth disease (HFMD) and fatal neurological disorders in some cases without effective treatment. Here we show that heat shock cognate protein 70 (Hsc70), a molecular chaperone, displays pivotal role in viral infections. Knockdown of Hsc70 significantly suppresses viral replication evidenced by reducing not only the level of both viral replication intermediates (negative stranded RNA) and viral genomic RNA (positive stranded RNA), but also the level of viral protein expression; whereas ectopic expression of Hsc70 markedly promotes viral replication...
November 24, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29167402/the-role-of-cysteine-string-protein-alpha-csp%C3%AE-phosphorylation-at-serine-10-and-34-by-protein-kinase-c%C3%AE-for-presynaptic-maintenance
#15
Toshihiko Shirafuji, Takehiko Ueyama, Naoko Adachi, Ken-Ichi Yoshino, Yusuke Sotomaru, Junsuke Uwada, Azumi Kaneoka, Taro Ueda, Shigeru Tanaka, Izumi Hide, Naoaki Saito, Norio Sakai
Protein Kinase Cγ (PKCγ) knockout (KO) animals exhibit symptoms of Parkinson's disease (PD), including dopaminergic neuronal loss in the substantia nigra. However, the PKCγ substrates responsible for the survival of dopaminergic neurons, in vivo, have not yet been elucidated. Previously, we found 10 potent substrates in the striatum of PKCγ-KO mice. Here, we focused on cysteine string protein alpha (CSPα), one of the proteins from the heat shock protein (HSP) 40 co-chaperone families localized on synaptic vesicles...
November 22, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29150658/differential-regulation-of-synaptic-ap-2-clathrin-vesicle-uncoating-in-synaptic-plasticity
#16
Ermes Candiello, Ratnakar Mishra, Bernhard Schmidt, Olaf Jahn, Peter Schu
AP-1/σ1B-deficiency causes X-linked intellectual disability. AP-1/σ1B -/- mice have impaired synaptic vesicle recycling, fewer synaptic vesicles and enhanced endosome maturation mediated by AP-1/σ1A. Despite defects in synaptic vesicle recycling synapses contain two times more endocytic AP-2 clathrin-coated vesicles. We demonstrate increased formation of two classes of AP-2/clathrin coated vesicles. One which uncoats readily and a second with a stabilised clathrin coat. Coat stabilisation is mediated by three molecular mechanisms: reduced recruitment of Hsc70 and synaptojanin1 and enhanced μ2/AP-2 phosphorylation and activation...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29145196/aqp2-abundance-is-regulated-by-the-e3-ligase-chip-via-hsp70
#17
Mariangela Centrone, Marianna Ranieri, Annarita Di Mise, Sante Princiero Berlingerio, Annamaria Russo, Peter M T Deen, Olivier Staub, Giovanna Valenti, Grazia Tamma
BACKGROUND/AIMS: AQP2 expression is mainly controlled by vasopressin-dependent changes in protein abundance which is in turn regulated by AQP2 ubiquitylation and degradation, however the proteins involved in these processes are largely unknown. Here, we investigated the potential role of the CHIP E3 ligase in AQP2 regulation. METHODS: MCD4 cells and kidney slices were used to study the involvement of the E3 ligase CHIP on AQP2 protein abundance by cell homogenization and immunoprecipitation followed by immunoblotting...
November 17, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29111393/cyclin-dependent-kinase-5-mediated-phosphorylation-of-chip-promotes-the-taif-dependent-death-pathway-in-rotenone-treated-cortical-neurons
#18
Chiho Kim, Juhyung Lee, Yeon Uk Ko, Young J Oh
Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase. Its dysregulation has been implicated in various neurodegenerative diseases. We previously reported that phosphorylation of the C-terminus of the Hsc70-interacting protein (CHIP) by Cdk5 promotes truncated apoptosis-inducing factor (tAIF)-mediated neuronal death induced by oxidative stress. Here, we determined whether this Cdk5-dependent cell death signaling pathway is present in experimental models of Parkinson's disease. First, we showed that rotenone activates Cdk5 in primary cultures of cortical neurons and causes tAIF-dependent neuronal cell death...
October 27, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29063205/steered-molecular-dynamics-simulation-of-the-binding-of-the-bovine-auxilin-j-domain-to-the-hsc70-nucleotide-binding-domain
#19
You-Lin Xue, Lei Zhou, Yuna Sun, Hui Li, Gary W Jones, Youtao Song
The Hsp70 and Hsp40 chaperone machine plays critical roles in protein folding, membrane translocation, and protein degradation by binding and releasing protein substrates in a process that utilizes ATP. The activities of the Hsp70 family of chaperones are recruited and stimulated by the J domains of Hsp40 chaperones. However, structural information on the Hsp40-Hsp70 complex is lacking, and the molecular details of this interaction are yet to be elucidated. Here we used steered molecular dynamics (SMD) simulations to investigate the molecular interactions that occur during the dissociation of the auxilin J domain from the Hsc70 nucleotide-binding domain (NBD)...
October 23, 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/29034430/ultraviolet-filters-and-heat-shock-proteins-effects-in-chironomus-riparius-by-benzophenone-3-and-4-methylbenzylidene-camphor
#20
Raquel Martín-Folgar, Mónica Aquilino, Irene Ozáez, José-Luis Martínez-Guitarte
Benzophenone-3 (BP3) and 4-methylbenzylidene camphor (4MBC) are common ultraviolet filters (UV filters), compounds considered as emergent contaminants, used in different products like plastics and personal care products. The levels of these compounds are rising in the wild, but the effects they have on invertebrates are poorly understood. Chironomus riparius is a benthic insect widely used in toxicology, and several studies have been previously performed in our laboratory to determine the effects these compounds have on this organism at the molecular level...
October 16, 2017: Environmental Science and Pollution Research International
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