Artificial targeting of misfolded cytosolic proteins to endoplasmic reticulum as a mechanism for clearance.

Abstract:

:We report that misfolded cytosolic proteins can be cleared from mammalian cells by directing them to endoplasmic reticulum (ER). NAT1 R64W and Parkin R42P are naturally occurring misfolded variants of cytosolic enzymes that acetylate arylamines and ubiquitinate proteins, respectively. We demonstrate that proteasome inhibition causes ER accumulation of NAT1 R64W and its ubiquitinated species, and that these products are cleared from cells following inhibition release. NAT1 WT by contrast is stable and not present at ER. The R42P mutation in Parkin locates to a UBL domain that interacts with C-terminal domains. Parkin R42P full length protein is trafficked poorly to ER and stable. Interestingly, fusion of the isolated R42P UBL to NAT1 WT results in a fusion product that is trafficked robustly to ER and degraded. Thus, the misfolded UBL is apparently masked by the intramolecular interactions. We also find that artificially directing Parkin R42P to ER by fusion with the Sec61β ER-directing transmembrane domain triggers its clearance. Altogether, our results suggest that routing misfolded cytosolic proteins to ER may be an effective strategy for clearance.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Liu F,Koepp DM,Walters KJ

doi

10.1038/srep12088

subject

Has Abstract

pub_date

2015-07-14 00:00:00

pages

12088

issn

2045-2322

pii

srep12088

journal_volume

5

pub_type

杂志文章
  • Noble-metal-free plasmonic photocatalyst: hydrogen doped semiconductors.

    abstract::The unique capacity of localized surface plasmon resonance (LSPR) offers a new opportunity to overcome the limited efficiency of semiconductor photocatalyst. Here we unravel that LSPR, which usually occurs in noble metal nanoparticles, can be realized by hydrogen doping in noble-metal-free semiconductor using TiO2 as ...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep03986

    authors: Ma X,Dai Y,Yu L,Huang B

    更新日期:2014-02-05 00:00:00

  • Multi-band MIM refractive index biosensor based on Ag-air grating with equivalent circuit and T-matrix methods in near-infrared region.

    abstract::In this paper, a multi-band metal-insulator-metal (MIM) perfect absorber with refractive index sensing capability has been investigated in near-infrared region. The proposed structure has been studied for biomedical applications such as detection of solution of glucose in water, diagnosis of different stages of malari...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-020-63459-w

    authors: Nejat M,Nozhat N

    更新日期:2020-04-14 00:00:00

  • Hot bodies protect amphibians against chytrid infection in nature.

    abstract::Environmental context strongly affects many host-pathogen interactions, but the underlying causes of these effects at the individual level are usually poorly understood. The amphibian chytrid fungus has caused amphibian population declines and extinctions in many parts of the world. Many amphibian species that have de...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep01515

    authors: Rowley JJ,Alford RA

    更新日期:2013-01-01 00:00:00

  • Genome-scale analysis identifies NEK2, DLGAP5 and ECT2 as promising diagnostic and prognostic biomarkers in human lung cancer.

    abstract::This study aims to identify promising biomarkers for the early detection of lung cancer and evaluate the prognosis of lung cancer patients. Genome-wide mRNA expression data obtained from the Gene Expression Omnibus (GSE19188, GSE18842 and GSE40791), including 231 primary tumor samples and 210 normal samples, were used...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-017-08615-5

    authors: Shi YX,Yin JY,Shen Y,Zhang W,Zhou HH,Liu ZQ

    更新日期:2017-08-14 00:00:00

  • Inter-cluster distance dependence of electrical conduction in nanocluster assembled films of silver: a new paradigm for design of nanostructures.

    abstract::The transport properties of films assembled from metal nanoclusters can be significantly different from the metals in their bulk or thin film forms due to quantum confinement effects and several competing energy and length scales. For a film composed of metal nanoclusters as its building blocks, the cluster size and t...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep07685

    authors: Bansal C,Praveen SG,Kumaran JT,Chatterjee A

    更新日期:2015-01-08 00:00:00

  • Calcium oxalate crystals increased enolase-1 secretion from renal tubular cells that subsequently enhanced crystal and monocyte invasion through renal interstitium.

    abstract::Calcium oxalate monohydrate (COM) crystals cause kidney stone disease by still unclear mechanisms. The present study aimed to characterize changes in secretion of proteins from basolateral compartment of renal tubular epithelial cells after exposure to COM crystals and then correlated them with the stone pathogenesis....

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep24064

    authors: Chiangjong W,Thongboonkerd V

    更新日期:2016-04-05 00:00:00

  • Results from 11C-metformin-PET scans, tissue analysis and cellular drug-sensitivity assays questions the view that biguanides affects tumor respiration directly.

    abstract::The anti-diabetic biguanide drugs metformin (METF) and phenformin (PHEN) may have anti-cancer effects. Biguanides suppress plasma growth factors, but nonetheless, the view that these mitochondrial inhibitors accumulate in tumor tissue to an extent that leads to severe energetic stress or alleviation of hypoxia-induced...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-017-10010-z

    authors: Iversen AB,Horsman MR,Jakobsen S,Jensen JB,Garm C,Jessen N,Breining P,Frøkiær J,Busk M

    更新日期:2017-08-25 00:00:00

  • Proteomic analysis of knee cartilage reveals potential signaling pathways in pathological mechanism of Kashin-Beck disease compared with osteoarthritis.

    abstract::The pathological mechanism of Kashin-Beck disease (KBD), an endemic osteoarthritic disease, remains to be poorly understood. This study was designed to identify signaling pathways and crucial proteins involved in the pathological mechanism of KBD compared with osteoarthritis (OA). The knee cartilage samples were colle...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-020-63932-6

    authors: Lei J,Amhare AF,Wang L,Lv Y,Deng H,Gao H,Guo X,Han J,Lammi MJ

    更新日期:2020-04-22 00:00:00

  • First fossil frog from Antarctica: implications for Eocene high latitude climate conditions and Gondwanan cosmopolitanism of Australobatrachia.

    abstract::Cenozoic ectothermic continental tetrapods (amphibians and reptiles) have not been documented previously from Antarctica, in contrast to all other continents. Here we report a fossil ilium and an ornamented skull bone that can be attributed to the Recent, South American, anuran family Calyptocephalellidae or helmeted ...

    journal_title:Scientific reports

    pub_type: 历史文章,杂志文章

    doi:10.1038/s41598-020-61973-5

    authors: Mörs T,Reguero M,Vasilyan D

    更新日期:2020-04-23 00:00:00

  • P38/MAPK contributes to endothelial barrier dysfunction via MAP4 phosphorylation-dependent microtubule disassembly in inflammation-induced acute lung injury.

    abstract::Excessive activation of inflammation and the accompanying lung vascular endothelial barrier disruption are primary pathogenic features of acute lung injury (ALI). Microtubule-associated protein 4 (MAP4), a tubulin assembly-promoting protein, is important for maintaining the microtubule (MT) cytoskeleton and cell-cell ...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep08895

    authors: Li L,Hu J,He T,Zhang Q,Yang X,Lan X,Zhang D,Mei H,Chen B,Huang Y

    更新日期:2015-03-09 00:00:00

  • Elevated troponin levels are associated with early neurological worsening in ischemic stroke with atrial fibrillation.

    abstract::Serum cardiac troponin I (cTnI) is often elevated in patients with ischemic stroke, and is associated with their prognosis. Since cTnI is also closely related to atrial fibrillation (AF), cTnI may be a sensitive prognostic indicator in patients with AF-related stroke. This study aimed to evaluate the association betwe...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-020-69303-5

    authors: Nam KW,Kim CK,Yu S,Chung JW,Bang OY,Kim GM,Jung JM,Song TJ,Kim YJ,Kim BJ,Heo SH,Park KY,Kim JM,Park JH,Choi JC,Park MS,Kim JT,Choi KH,Hwang YH,Seo WK,Oh K

    更新日期:2020-07-28 00:00:00

  • Load partitioning between the bcc-iron matrix and NiAl-type precipitates in a ferritic alloy on multiple length scales.

    abstract::An understanding of load sharing among constituent phases aids in designing mechanical properties of multiphase materials. Here we investigate load partitioning between the body-centered-cubic iron matrix and NiAl-type precipitates in a ferritic alloy during uniaxial tensile tests at 364 and 506 °C on multiple length ...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep23137

    authors: Sun Z,Song G,Sisneros TA,Clausen B,Pu C,Li L,Gao Y,Liaw PK

    更新日期:2016-03-16 00:00:00

  • Weak stromal Caveolin-1 expression in colorectal liver metastases predicts poor prognosis after hepatectomy for liver-only colorectal metastases.

    abstract::Loss of stromal Caveolin-1 (CAV1) expression is associated with poor prognosis in various cancers. We evaluated the prognostic value of CAV1 expression of both cancer cells and stromal cells in colorectal liver metastases (CRLM) in patients undergoing hepatectomy. In this retrospective study, 109 patients were enrolle...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-017-02251-9

    authors: Neofytou K,Pikoulis E,Petrou A,Agrogiannis G,Petrides C,Papakonstandinou I,Papalambros A,Aggelou A,Kavatzas N,Liakakos T,Felekouras E

    更新日期:2017-05-17 00:00:00

  • Comparative temporal metabolomics studies to investigate interspecies variation in three Ocimum species.

    abstract::Ocimum is one of the most revered medicinally useful plants which have various species. Each of the species is distinct in terms of metabolite composition as well as the medicinal property. Some basil types are used more often as an aromatic and flavoring ingredient. It would be informative to know relatedness among t...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-020-61957-5

    authors: Rastogi S,Shah S,Kumar R,Kumar A,Shasany AK

    更新日期:2020-03-23 00:00:00

  • Altered regional homogeneity and functional brain networks in Type 2 diabetes with and without mild cognitive impairment.

    abstract::Patients with Type-2 Diabetes Mellitus (T2DM) have a considerably higher risk of developing mild cognitive impairment (MCI) and dementia. The initial symptoms are very insidious at onset. We investigated the alterations in spontaneous brain activity and network connectivity through regional homogeneity (ReHo) and grap...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-020-76495-3

    authors: Xiong Y,Chen X,Zhao X,Fan Y,Zhang Q,Zhu W

    更新日期:2020-12-04 00:00:00

  • Fingerprinting breast cancer vs. normal mammary cells by mass spectrometric analysis of volatiles.

    abstract::There is increasing interest in the development of noninvasive diagnostic methods for early cancer detection, to improve the survival rate and quality of life of cancer patients. Identification of volatile metabolic compounds may provide an approach for noninvasive early diagnosis of malignant diseases. Here we analyz...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep05196

    authors: He J,Sinues PM,Hollmén M,Li X,Detmar M,Zenobi R

    更新日期:2014-06-06 00:00:00

  • Resource prioritization and balancing for the quantum internet.

    abstract::The quantum Internet enables networking based on the fundamentals of quantum mechanics. Here, methods and procedures of resource prioritization and resource balancing are defined for the quantum Internet. We define a model for resource consumption optimization in quantum repeaters, and a strongly-entangled network str...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-020-78960-5

    authors: Gyongyosi L,Imre S

    更新日期:2020-12-28 00:00:00

  • Author Correction: A novel perspective on MOL-PCR optimization and MAGPIX analysis of in-house multiplex foodborne pathogens detection assay.

    abstract::A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper. ...

    journal_title:Scientific reports

    pub_type: 已发布勘误

    doi:10.1038/s41598-019-42194-x

    authors: Reslova N,Huvarova V,Hrdy J,Kasny M,Kralik P

    更新日期:2019-04-04 00:00:00

  • Relating quantum coherence and correlations with entropy-based measures.

    abstract::Quantum coherence and quantum correlations are important quantum resources for quantum computation and quantum information. In this paper, using entropy-based measures, we investigate the relationships between quantum correlated coherence, which is the coherence between subsystems, and two main kinds of quantum correl...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-017-09332-9

    authors: Wang XL,Yue QL,Yu CH,Gao F,Qin SJ

    更新日期:2017-09-21 00:00:00

  • Differential roles of caspase-1 and caspase-11 in infection and inflammation.

    abstract::Caspase-1, also known as interleukin-1β (IL-1β)-converting enzyme (ICE), regulates antimicrobial host defense, tissue repair, tumorigenesis, metabolism and membrane biogenesis. On activation within an inflammasome complex, caspase-1 induces pyroptosis and converts pro-IL-1β and pro-IL-18 into their biologically active...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep45126

    authors: Man SM,Karki R,Briard B,Burton A,Gingras S,Pelletier S,Kanneganti TD

    更新日期:2017-03-27 00:00:00

  • Arsenic resistance strategy in Pantoea sp. IMH: Organization, function and evolution of ars genes.

    abstract::Pantoea sp. IMH is the only bacterium found in genus Pantoea with a high As resistance capacity, but its molecular mechanism is unknown. Herein, the organization, function, and evolution of ars genes in IMH are studied starting with analysis of the whole genome. Two ars systems - ars1 (arsR1B1C1H1) and ars2 (arsR2B2C2...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep39195

    authors: Wang L,Zhuang X,Zhuang G,Jing C

    更新日期:2016-12-14 00:00:00

  • Structural and functional studies of a noncanonical Dicer from Entamoeba histolytica.

    abstract::RNaseIII proteins are dsRNA-specific endonucleases involved in many important biological processes, such as small RNA processing and maturation in eukaryotes. Various small RNAs have been identified in a protozoan parasite Entamoeba histolytica. EhRNaseIII is the only RNaseIII endonuclease domain (RIIID)-containing pr...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep44832

    authors: Yu X,Li X,Zheng L,Ma J,Gan J

    更新日期:2017-03-20 00:00:00

  • Integrative analysis of genomic sequencing data reveals higher prevalence of LRP1B mutations in lung adenocarcinoma patients with COPD.

    abstract::Both chronic Obstruction Pulmonary Disease (COPD) and lung cancer are leading causes of death globally. Although COPD and lung cancer coexist frequently, it is unknown whether lung cancer patients with COPD harbor distinct genomic characteristics compared to those without COPD. In this study, we retrospectively analyz...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-017-02405-9

    authors: Xiao D,Li F,Pan H,Liang H,Wu K,He J

    更新日期:2017-05-18 00:00:00

  • Risk factors for postoperative haemorrhage after total thyroidectomy: clinical results based on 2,678 patients.

    abstract::The aim of this study was to analyse postoperative haemorrhage (POH) after a total thyroidectomy and explore the possible risk factors. Records of patients receiving a total thyroidectomy were reviewed and analysed for risk factors of POH. From the 2,678 patients in this study, a total of 39 patients had POH, represen...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-017-07334-1

    authors: Zhang X,Du W,Fang Q

    更新日期:2017-08-01 00:00:00

  • Scanning electron microscopy and machine learning reveal heterogeneity in capsular morphotypes of the human pathogen Cryptococcus spp.

    abstract::Phenotypic heterogeneity is an important trait for the development and survival of many microorganisms including the yeast Cryptococcus spp., a deadly pathogen spread worldwide. Here, we have applied scanning electron microscopy (SEM) to define four Cryptococcus spp. capsule morphotypes, namely Regular, Spiky, Bald, a...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-020-59276-w

    authors: Lopes W,Cruz GNF,Rodrigues ML,Vainstein MH,Kmetzsch L,Staats CC,Vainstein MH,Schrank A

    更新日期:2020-02-11 00:00:00

  • Transient autonomic responses during sustained attention in high and low fit young adults.

    abstract::Maintaining vigilance over long periods of time is especially critical in performing fundamental everyday activities and highly responsible professional tasks (e.g., driving, performing surgery or piloting). Here, we investigated the role of aerobic fitness as a crucial factor related to the vigilance capacity. To thi...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep27556

    authors: Luque-Casado A,Perakakis P,Ciria LF,Sanabria D

    更新日期:2016-06-08 00:00:00

  • Randomized, Multicenter, Double-Blind Study of the Safety and Efficacy of 1%D-3-Hydroxybutyrate eye drops for Dry Eye Disease.

    abstract::In a previous study, we demonstrated that topical D-beta-hydroxybutyrate ameliorates corneal epithelial erosion and superficial punctate keratopathy in a rat model of dry eye disease. In the current investigation, we performed a prospective, randomized, multicentre, double-blind, placebo-controlled study to assess the...

    journal_title:Scientific reports

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1038/srep20855

    authors: Kawakita T,Uchino M,Fukagawa K,Yoshino K,Shimazaki S,Toda I,Tanaka M,Arai H,Sakatani K,Hata S,Okano T,Tsubota K

    更新日期:2016-02-11 00:00:00

  • Budgerigars adopt robust, but idiosyncratic flight paths.

    abstract::We have investigated the paths taken by Budgerigars while flying in a tunnel. The flight trajectories of nine Budgerigars (Melopsittacus undulatus) were reconstructed in 3D from high speed stereo videography of their flights in an obstacle-free tunnel. Individual birds displayed highly idiosyncratic flight trajectorie...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-020-59013-3

    authors: Karmaker D,Groening J,Wilson M,Schiffner I,Srinivasan MV

    更新日期:2020-02-13 00:00:00

  • Large-Scale Analysis of Drug Side Effects via Complex Regulatory Modules Composed of microRNAs, Transcription Factors and Gene Sets.

    abstract::Identifying the occurrence mechanism of drug-induced side effects (SEs) is critical for design of drug target and new drug development. The expression of genes in biological processes is regulated by transcription factors(TFs) and/or microRNAs. Most of previous studies were focused on a single level of gene or gene se...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-017-06083-5

    authors: Jia X,Jin Q,Liu X,Bian X,Wang Y,Liu L,Ma H,Tan F,Gu M,Chen X

    更新日期:2017-07-20 00:00:00

  • Investigation and Restoration of BEST1 Activity in Patient-derived RPEs with Dominant Mutations.

    abstract::BEST1 is a Ca2+-activated Cl- channel predominantly expressed in retinal pigment epithelium (RPE), and over 250 genetic mutations in the BEST1 gene have been identified to cause retinal degenerative disorders generally known as bestrophinopathies. As most BEST1 mutations are autosomal dominant, it is of great biomedic...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-019-54892-7

    authors: Ji C,Li Y,Kittredge A,Hopiavuori A,Ward N,Yao P,Fukuda Y,Zhang Y,Tsang SH,Yang T

    更新日期:2019-12-13 00:00:00