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chip hsp70 interacting protein

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https://www.readbyqxmd.com/read/29714053/sulforaphane-upregulates-the-heat-shock-protein-co-chaperone-chip-and-clears-amyloid-%C3%AE-and-tau-in-a-mouse-model-of-alzheimer-s-disease
#1
Siyoung Lee, Bo-Ryoung Choi, Jisung Kim, Frank M LaFerla, Jung Han Yoon Park, Jung-Soo Han, Ki Won Lee, Jiyoung Kim
SCOPE: Sulforaphane is an herbal isothiocyanate enriched in cruciferous vegetables. Here, we investigated whether sulforaphane modulates the production of amyloid-β (Aβ) and tau, the two main pathological factors in Alzheimer's disease (AD). METHODS AND RESULTS: A triple transgenic mouse model of AD (3 × Tg-AD) was used to study the effect of sulforaphane. Oral gavage of sulforaphane reduced protein levels of monomeric and polymeric forms of Aβ as well as tau and phosphorylated tau in 3 × Tg-AD mice...
April 30, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29686000/angiotensin-ii-promotes-k-v-7-4-channels-degradation-through-reduced-interaction-with-hsp90-heat-shock-protein-90
#2
Vincenzo Barrese, Jennifer B Stott, Hericka B Figueiredo, Aisah A Aubdool, Adrian J Hobbs, Thomas A Jepps, Alister J McNeish, Iain A Greenwood
Voltage-gated Kv 7.4 channels have been implicated in vascular smooth muscle cells' activity because they modulate basal arterial contractility, mediate responses to endogenous vasorelaxants, and are downregulated in several arterial beds in different models of hypertension. Angiotensin II (Ang II) is a key player in hypertension that affects the expression of several classes of ion channels. In this study, we evaluated the effects of Ang II on the expression and function of vascular Kv 7.4. Western blot and quantitative polymerase chain reaction revealed that in whole rat mesenteric artery, Ang II incubation for 1 to 7 hours decreased Kv 7...
April 23, 2018: Hypertension
https://www.readbyqxmd.com/read/29685889/wwp2-is-a-physiological-ubiquitin-ligase-for-phosphatase-and-tensin-homolog-pten-in-mice
#3
Hongchang Li, Pengfei Zhang, Qiuyue Zhang, Chaonan Li, Weiguo Zou, Zhijie Chang, Chun-Ping Cui, Lingqiang Zhang
The tumor suppressor phosphatase and tensin homolog (PTEN) plays a central role in regulating phosphatidylinositol-3-kinase (PI3K) signaling, and its gene is very frequently mutated in various human cancers. Numerous studies have revealed that PTEN levels are tightly regulated by both transcriptional and post-translational modifications, with especially ubiquitylation significantly regulating PTEN protein levels. Although several ubiquitin ligases have been reported to mediate PTEN ubiquitylation in vitro , the ubiquitin ligase that promotes PTEN degradation in vivo has not been reported...
April 23, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29619270/chip-regulates-bone-mass-by-targeting-multiple-traf-family-members-in-bone-marrow-stromal-cells
#4
Tingyu Wang, Shan Li, Dan Yi, Guang-Qian Zhou, Zhijie Chang, Peter X Ma, Guozhi Xiao, Di Chen
Carboxyl terminus of Hsp70-interacting protein (CHIP or STUB1) is an E3 ligase and regulates the stability of several proteins which are involved in different cellular functions. Our previous studies demonstrated that Chip deficient mice display bone loss phenotype due to increased osteoclast formation through enhancing TRAF6 activity in osteoclasts. In this study we provide novel evidence about the function of CHIP. We found that osteoblast differentiation and bone formation were also decreased in Chip KO mice...
2018: Bone Research
https://www.readbyqxmd.com/read/29565056/protein-cross-linking-capillary-electrophoresis-at-increased-throughput-for-a-range-of-protein-protein-interactions
#5
Claire M Ouimet, Mohamed Dawod, James Grinias, Victoria A Assimon, Jean Lodge, Anna K Mapp, Jason E Gestwicki, Robert T Kennedy
Tools for measuring affinities and stoichiometries of protein-protein complexes are valuable for elucidating the role of protein-protein interactions (PPIs) in governing cell functions and screening for PPI modulators. Such measurements can be challenging because PPIs can span a wide range of affinities and include stoichiometries from dimers to high order oligomers. Also, most techniques require large amounts of protein which can hamper research for difficult to obtain proteins. Protein cross-linking capillary electrophoresis (PXCE) has the potential to directly measure PPIs and even resolve multiple PPIs while consuming attomole quantities...
March 22, 2018: Analyst
https://www.readbyqxmd.com/read/29511337/post-translational-modification-of-oct4-in-breast-cancer-tumorigenesis
#6
Yunhee Cho, Hyeok Gu Kang, Seok-Jun Kim, Seul Lee, Sujin Jee, Sung Gwe Ahn, Min Jueng Kang, Joon Seon Song, Joon-Yong Chung, Eugene C Yi, Kyung-Hee Chun
Recurrence and drug resistance of breast cancer are still the main reasons for breast cancer-associated deaths. Cancer stem cell (CSC) model has been proposed as a hypothesis for the lethality of breast cancer. Molecular mechanisms underlying CSC maintenance are still unclear. In this study, we generated mammospheres derived from breast cancer MDA-MB231 cells and MCF7 cells to enrich CSCs and performed DNA microarray analysis. We found that the expression of carboxy terminus of HSP70-interacting protein (CHIP) E3 ubiquitin ligase was significantly downregulated in breast CSCs...
March 6, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29367604/covalent-isg15-conjugation-to-chip-promotes-its-ubiquitin-e3-ligase-activity-and-inhibits-lung-cancer-cell-growth-in-response-to-type-i-interferon
#7
Lang Yoo, A-Rum Yoon, Chae-Ok Yun, Kwang Chul Chung
The carboxyl terminus of Hsp70-interacting protein (CHIP) acts as a ubiquitin E3 ligase and a link between the chaperones Hsp70/90 and the proteasome system, playing a vital role in maintaining protein homeostasis. CHIP regulates a number of proteins involved in a myriad of physiological and pathological processes, but the underlying mechanism of action via posttranslational modification has not been extensively explored. In this study, we investigated a novel modulatory mode of CHIP and its effect on CHIP enzymatic activity...
January 24, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29274099/effects-of-celastrol-on-tau-hyperphosphorylation-and-expression-of-hsf-1-and-hsp70-in-sh-sy5y-neuroblastoma-cells-induced-by-amyloid-%C3%AE-peptides
#8
Fanfan Cao, Ying Wang, Bin Peng, Xue Zhang, Denghai Zhang, Limin Xu
To observe the effects of celastrol on Tau hyperphosphorylation induced by amyloid-β peptides (Aβ) in SH-SY5Y neuroblastoma cells, the changes of Tau hyperphosphorylation and the expression of heat shock protein 90 (HSP90), HSP70, and heat shock factor 1 (HSF-1) in SH-SY5Y cells treated with Aβ1-42 and celastrol were measured. Tau hyperphosphorylation and HSP90 expression induced by Aβ1-42 was also measured by Western blotting after HSP70 or HSF-1 knockdown by siRNA. The interaction between HSP70 and Tau or HSP70 and carboxyl terminus of HSP70 interacting protein (CHIP) was measured by co-immunoprecipitation...
December 22, 2017: Biotechnology and Applied Biochemistry
https://www.readbyqxmd.com/read/29242247/chip-regulates-aquaporin-2-quality-control-and-body-water-homeostasis
#9
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 t 1/2 and reduced AQP2 ubiquitylation, resulting in greater levels of AQP2 and phosphorylated AQP2...
March 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29203715/the-role-of-heat-shock-proteins-and-co-chaperones-in-heart-failure
#10
REVIEW
Mark J Ranek, Marisa J Stachowski, Jonathan A Kirk, Monte S Willis
The ongoing contractile and metabolic demands of the heart require a tight control over protein quality control, including the maintenance of protein folding, turnover and synthesis. In heart disease, increases in mechanical and oxidative stresses, post-translational modifications (e.g., phosphorylation), for example, decrease protein stability to favour misfolding in myocardial infarction, heart failure or ageing. These misfolded proteins are toxic to cardiomyocytes, directly contributing to the common accumulation found in human heart failure...
January 19, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29145196/aqp2-abundance-is-regulated-by-the-e3-ligase-chip-via-hsp70
#11
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...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29091030/chip-as-a-membrane-shuttling-proteostasis-sensor
#12
Yannick Kopp, Wei-Han Lang, Tobias B Schuster, Adrián Martínez-Limón, Harald F Hofbauer, Robert Ernst, Giulia Calloni, R Martin Vabulas
Cells respond to protein misfolding and aggregation in the cytosol by adjusting gene transcription and a number of post-transcriptional processes. In parallel to functional reactions, cellular structure changes as well; however, the mechanisms underlying the early adaptation of cellular compartments to cytosolic protein misfolding are less clear. Here we show that the mammalian ubiquitin ligase C-terminal Hsp70-interacting protein (CHIP), if freed from chaperones during acute stress, can dock on cellular membranes thus performing a proteostasis sensor function...
November 1, 2017: ELife
https://www.readbyqxmd.com/read/29075633/structure-and-interactions-of-the-tpr-domain-of-sgt2-with-yeast-chaperones-and-ybr137wp
#13
Ewelina M Krysztofinska, Nicola J Evans, Arjun Thapaliya, James W Murray, Rhodri M L Morgan, Santiago Martinez-Lumbreras, Rivka L Isaacson
Small glutamine-rich tetratricopeptide repeat-containing protein 2 (Sgt2) is a multi-module co-chaperone involved in several protein quality control pathways. The TPR domain of Sgt2 and several other proteins, including SGTA, Hop, and CHIP, is a highly conserved motif known to form transient complexes with molecular chaperones such as Hsp70 and Hsp90. In this work, we present the first high resolution crystal structures of Sgt2_TPR alone and in complex with a C-terminal peptide PTVEEVD from heat shock protein, Ssa1...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28757353/osmotic-and-heat-stress-dependent-regulation-of-mlk4%C3%AE-and-mlk3-by-the-chip-e3-ligase-in-ovarian-cancer-cells
#14
Natalya A Blessing, Srimathi Kasturirangan, Evan M Zink, April L Schroyer, Deborah N Chadee
Mixed Lineage Kinase 3 (MLK3), a member of the MLK subfamily of protein kinases, is a mitogen-activated protein (MAP) kinase kinase kinase (MAP3K) that activates MAPK signalling pathways and regulates cellular responses such as proliferation, invasion and apoptosis. MLK4β, another member of the MLK subfamily, is less extensively studied, and the regulation of MLK4β by stress stimuli is not known. In this study, the regulation of MLK4β and MLK3 by osmotic stress, thermostress and heat shock protein 90 (Hsp90) inhibition was investigated in ovarian cancer cells...
November 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28593150/the-antitumor-effect-of-c-terminus-of-hsp70-interacting-protein-via-degradation-of-c-met-in-small-cell-lung-cancer
#15
Sung Ho Cho, Jong In Kim, Hyun Su Kim, Sung Dal Park, Kang Won Jang
BACKGROUND: The mesenchymal-epithelial transition factor (MET) receptor can be overexpressed in solid tumors, including small cell lung cancer (SCLC). However, the molecular mechanism regulating MET stability and turnover in SCLC remains undefined. One potential mechanism of MET regulation involves the C-terminus of Hsp70-interacting protein (CHIP), which targets heat shock protein 90-interacting proteins for ubiquitination and proteasomal degradation. In the present study, we investigated the functional effects of CHIP expression on MET regulation and the control of SCLC cell apoptosis and invasion...
June 2017: Korean Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28574736/multiple-functions-of-the-e3-ubiquitin-ligase-chip-in-immunity
#16
Shaohua Zhan, Tianxiao Wang, Wei Ge
The carboxyl terminal of Hsp70-interacting protein (CHIP) is an E3 ubiquitin ligase that plays a pivotal role in the protein quality control system by shifting the balance of the folding-refolding machinery toward the degradative pathway. However, the precise mechanisms by which nonnative proteins are selected for degradation by CHIP either directly or indirectly via chaperone Hsp70 or Hsp90 are still not clear. In this review, we aim to provide a comprehensive model of the mechanism by which CHIP degrades its substrate in a chaperone-dependent or direct manner...
September 3, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/28536143/aurora-kinase-a-promotes-ar-degradation-via-the-e3-ligase-chip
#17
Sukumar Sarkar, David L Brautigan, James M Larner
Reducing the levels of the androgen receptor (AR) is one of the most viable approaches to combat castration-resistant prostate cancer. Previously, we observed that proteasomal-dependent degradation of AR in response to 2-methoxyestradiol (2-ME) depends primarily on the E3 ligase C-terminus of HSP70-interacting protein (STUB1/CHIP). Here, 2-ME stimulation activates CHIP by phosphorylation via Aurora kinase A (AURKA). Aurora A kinase inhibitors and RNAi knockdown of Aurora A transcript selectively blocked CHIP phosphorylation and AR degradation...
August 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28441527/proteostasis-or-aging-let-the-chips-fall-where-they-may
#18
REVIEW
Robyn Branicky, Siegfried Hekimi
The conserved E3 ubiquitin ligase CHIP/CHN-1 contributes to proteostasis by ubiquitylating HSP70 and HSP90-interacting proteins. In a recent issue of Cell,Tawo et al. (2017) show that CHIP/CHN-1 also directly ubiquitylates the insulin receptor INSR/DAF-2 to regulate its turnover. These findings suggest an unexpected interpretation of the effects of altered proteostasis on survival.
April 24, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28337377/the-e3-ubiquitin-ligase-chip-mir-92b-pten-regulatory-network-contributes-to-tumorigenesis-of-glioblastoma
#19
Tao Xu, Hongxiang Wang, Mei Jiang, Yong Yan, Weiqing Li, Hanchong Xu, Qilin Huang, Yicheng Lu, Juxiang Chen
Glioblastoma (GBM) is the most frequent, aggressive and fatal tumor in the central nervous system, while PTEN signaling is frequently deregulated in human GBM. We previously reported the up-regulation of the carboxyl terminal of Hsp70-interacting protein (CHIP) in GBM, however, the causal link between its dysregulation and tumorigenesis has not been established. Using miRNA microarrays and quantitative RT-PCR (qRT-PCR), we found activation of CHIP leads to increased transcription of miR-92b. Further studies in T98G and LN229 cells showed overexpression of miR-92b elicited reduction of PTEN and efficiently rescued glioma development in CHIP knock-down cells...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28320739/a-covalently-bound-inhibitor-triggers-ezh2-degradation-through-chip-mediated-ubiquitination
#20
Xu Wang, Wei Cao, Jianjun Zhang, Ming Yan, Qin Xu, Xiangbing Wu, Lixin Wan, Zhiyuan Zhang, Chenping Zhang, Xing Qin, Meng Xiao, Dongxia Ye, Yuyang Liu, Zeguang Han, Shaomeng Wang, Li Mao, Wenyi Wei, Wantao Chen
Enhancer of zeste homolog 2 (EZH2) has been characterized as a critical oncogene and a promising drug target in human malignant tumors. The current EZH2 inhibitors strongly suppress the enhanced enzymatic function of mutant EZH2 in some lymphomas. However, the recent identification of a PRC2- and methyltransferase-independent role of EZH2 indicates that a complete suppression of all oncogenic functions of EZH2 is needed. Here, we report a unique EZH2-targeting strategy by identifying a gambogenic acid (GNA) derivative as a novel agent that specifically and covalently bound to Cys668 within the EZH2-SET domain, triggering EZH2 degradation through COOH terminus of Hsp70-interacting protein (CHIP)-mediated ubiquitination...
May 2, 2017: EMBO Journal
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