当前位置： SCI文献检索 > Protein & Cell期刊下所有文献 > Expression of human FUS/TLS in yeast leads to protein aggregation and cytotoxicity, recapitulating key features of FUS proteinopathy.

Expression of human FUS/TLS in yeast leads to protein aggregation and cytotoxicity, recapitulating key features of FUS proteinopathy.

Abstract：

:Mutations in the fused in sarcoma/translocated in liposarcoma (FUS/TLS) gene have been associated with amyotrophic lateral sclerosis (ALS). FUS-positive neuropathology is reported in a range of neurodegenerative diseases, including ALS and fronto-temporal lobar degeneration with ubiquitin-positive pathology (FTLDU). To examine protein aggregation and cytotoxicity, we expressed human FUS protein in yeast. Expression of either wild type or ALS-associated R524S or P525L mutant FUS in yeast cells led to formation of aggregates and cytotoxicity, with the two ALS mutants showing increased cytotoxicity. Therefore, yeast cells expressing human FUS protein recapitulate key features of FUS-positive neurodegenerative diseases. Interestingly, a significant fraction of FUS expressing yeast cells stained by propidium iodide were without detectable protein aggregates, suggesting that membrane impairment and cellular damage caused by FUS expression may occur before protein aggregates become microscopically detectable and that aggregate formation might protect cells from FUS-mediated cytotoxicity. The N-terminus of FUS, containing the QGSY and G rich regions, is sufficient for the formation of aggregates but not cytotoxicity. The C-terminal domain, which contains a cluster of mutations, did not show aggregation or cytotoxicity. Similar to TDP-43 when expressed in yeast, FUS protein has the intrinsic property of forming aggregates in the absence of other human proteins. On the other hand, the aggregates formed by FUS are thioflavin T-positive and resistant to 0.5% sarkosyl, unlike TDP-43 when expressed in yeast cells. Furthermore, TDP-43 and FUS display distinct domain requirements in aggregate formation and cytotoxicity.

journal_name

Protein Cell

journal_title

Protein & cell

authors

Fushimi K,Long C,Jayaram N,Chen X,Li L,Wu JY

doi

10.1007/s13238-011-1014-5

subject

Has Abstract

pub_date

2011-02-01 00:00:00

pages

141-9

issue

2

eissn

1674-800X

issn

1674-8018

journal_volume

2

pub_type

杂志文章

相关文献

Protein & Cell文献大全
  • The evolving landscape in the therapy of acute myeloid leukemia.

    abstract：:Acute myeloid leukemia (AML) is a heterogeneous clonal disorder of myeloid precursors arrested in their maturation, creating a diverse disease entity with a wide range of responses to historically standard treatment approaches. While significant progress has been made in characterizing and individualizing the disease ...

    journal_title：Protein & cell

    pub_type： 杂志文章,评审

    doi：10.1007/s13238-013-3057-2

    authors： Peloquin GL,Chen YB,Fathi AT

    更新日期：2013-10-01 00:00:00

  • Correction to: Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2.

    abstract：:In the original publication the author's name 'Dimitri Lavillete' is published incorrectly. The correct author name should be spelt as 'Dimitri Lavillette' is provided in this correction. ...

    journal_title：Protein & cell

    pub_type： 已发布勘误

    doi：10.1007/s13238-020-00801-y

    authors： Xiong R,Zhang L,Li S,Sun Y,Ding M,Wang Y,Zhao Y,Wu Y,Shang W,Jiang X,Shan J,Shen Z,Tong Y,Xu L,Chen Y,Liu Y,Zou G,Lavillette D,Zhao Z,Wang R,Zhu L,Xiao G,Lan K,Li H,Xu K

    更新日期：2020-11-09 00:00:00

  • SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3-TBK1 complex.

    abstract：:SARS coronavirus (SARS-CoV) develops an antagonistic mechanism by which to evade the antiviral activities of interferon (IFN). Previous studies suggested that SARS-CoV papain-like protease (PLpro) inhibits activation of the IRF3 pathway, which would normally elicit a robust IFN response, but the mechanism(s) used by S...

    journal_title：Protein & cell

    pub_type： 杂志文章

    doi：10.1007/s13238-014-0026-3

    authors： Chen X,Yang X,Zheng Y,Yang Y,Xing Y,Chen Z

    更新日期：2014-05-01 00:00:00

  • Structures of the N- and C-terminal domains of MHV-A59 nucleocapsid protein corroborate a conserved RNA-protein binding mechanism in coronavirus.

    abstract：:Coronaviruses are the causative agent of respiratory and enteric diseases in animals and humans. One example is SARS, which caused a worldwide health threat in 2003. In coronaviruses, the structural protein N (nucleocapsid protein) associates with the viral RNA to form the filamentous nucleocapsid and plays a crucial ...

    journal_title：Protein & cell

    pub_type： 杂志文章

    doi：10.1007/s13238-010-0079-x

    authors： Ma Y,Tong X,Xu X,Li X,Lou Z,Rao Z

    更新日期：2010-07-01 00:00:00

  • Crystal structures of the two membrane-proximal Ig-like domains (D3D4) of LILRB1/B2: alternative models for their involvement in peptide-HLA binding.

    abstract：:Leukocyte immunoglobulin-like receptors (LILRs), also called CD85s, ILTs, or LIRs, are important mediators of immune activation and tolerance that contain tandem immunoglobulin (Ig)-like folds. There are 11 (in addition to two pseudogenes) LILRs in total, two with two Ig-like domains (D1D2) and the remaining nine with...

    journal_title：Protein & cell

    pub_type： 杂志文章

    doi：10.1007/s13238-013-3908-x

    authors： Nam G,Shi Y,Ryu M,Wang Q,Song H,Liu J,Yan J,Qi J,Gao GF

    更新日期：2013-10-01 00:00:00

  • Secreted miR-34a in astrocytic shedding vesicles enhanced the vulnerability of dopaminergic neurons to neurotoxins by targeting Bcl-2.

    abstract：:MicroRNAs (miRNAs) are a class of noncoding RNAs that regulates target gene expression at posttranscriptional level, leading to further biological functions. We have demonstrated that microvesicles (MVs) can deliver miRNAs into target cells as a novel way of intercellular communication. It is reported that in central ...

    journal_title：Protein & cell

    pub_type： 杂志文章

    doi：10.1007/s13238-015-0168-y

    authors： Mao S,Sun Q,Xiao H,Zhang C,Li L

    更新日期：2015-07-01 00:00:00

  • Atg7 in development and disease: panacea or Pandora's Box?

    abstract：:Macroautophagy is an evolutionarily conserved intracellular degradation system used by life ranging from yeasts to mammals. The core autophagic machinery is composed of ATG (autophagy-related) protein constituents. One particular member of the ATG protein family, Atg7, has been the focus of recent research. Atg7 acts ...

    journal_title：Protein & cell

    pub_type： 杂志文章,评审

    doi：10.1007/s13238-015-0195-8

    authors： Xiong J

    更新日期：2015-10-01 00:00:00

  • Rescue of premature aging defects in Cockayne syndrome stem cells by CRISPR/Cas9-mediated gene correction.

    abstract：:Cockayne syndrome (CS) is a rare autosomal recessive inherited disorder characterized by a variety of clinical features, including increased sensitivity to sunlight, progressive neurological abnormalities, and the appearance of premature aging. However, the pathogenesis of CS remains unclear due to the limitations of ...

    journal_title：Protein & cell

    pub_type： 杂志文章

    doi：10.1007/s13238-019-0623-2

    authors： Wang S,Min Z,Ji Q,Geng L,Su Y,Liu Z,Hu H,Wang L,Zhang W,Suzuiki K,Huang Y,Zhang P,Tang TS,Qu J,Yu Y,Liu GH,Qiao J

    更新日期：2020-01-01 00:00:00

  • Molecular basis for the inhibition of β-hydroxyacyl-ACP dehydratase HadAB complex from Mycobacterium tuberculosis by flavonoid inhibitors.

    abstract：:Dehydration is one of the key steps in the biosynthesis of mycolic acids and is vital to the growth of Mycobacterium tuberculosis (Mtb). Consequently, stalling dehydration cures tuberculosis (TB). Clinically used anti-TB drugs like thiacetazone (TAC) and isoxyl (ISO) as well as flavonoids inhibit the enzyme activity o...

    journal_title：Protein & cell

    pub_type： 杂志文章

    doi：10.1007/s13238-015-0181-1

    authors： Dong Y,Qiu X,Shaw N,Xu Y,Sun Y,Li X,Li J,Rao Z

    更新日期：2015-07-01 00:00:00

  • New discovery rarely runs smooth: an update on progranulin/TNFR interactions.

    abstract：:Progranulin (PGRN) is a growth factor implicated in various pathophysiological processes, including wound healing, inflammation, tumorigenesis, and neurodegeneration. It was previously reported that PGRN binds to tumor necrosis factor receptors (TNFR) and has therapeutic effects in inflammatory arthritis (Tang et. al,...

    journal_title：Protein & cell

    pub_type： 杂志文章,评审

    doi：10.1007/s13238-015-0213-x

    authors： Wang BC,Liu H,Talwar A,Jian J

    更新日期：2015-11-01 00:00:00

  • Correction to: A binding-block ion selective mechanism revealed by a Na/K selective channel.

    abstract：:In the original publication the PDB numbers were not cited. ...

    journal_title：Protein & cell

    pub_type： 已发布勘误

    doi：10.1007/s13238-019-0619-y

    authors： Yu J,Zhang B,Zhang Y,Xu CQ,Zhuo W,Ge J,Li J,Gao N,Li Y,Yang M

    更新日期：2019-07-01 00:00:00

  • Complement activation by phospholipids: the interplay of factor H and C1q.

    abstract：:Complement proteins in blood recognize charged particles. The anionic phospholipid (aPL) cardiolipin binds both complement proteins C1q and factor H. C1q is an activator of the complement classical pathway, while factor H is an inhibitor of the alternative pathway. To examine opposing effects of C1q and factor H on co...

    journal_title：Protein & cell

    pub_type： 杂志文章

    doi：10.1007/s13238-010-0125-8

    authors： Tan LA,Yu B,Sim FC,Kishore U,Sim RB

    更新日期：2010-11-01 00:00:00

  • Domesticated cynomolgus monkey embryonic stem cells allow the generation of neonatal interspecies chimeric pigs.

    abstract：:Blastocyst complementation by pluripotent stem cell (PSC) injection is believed to be the most promising method to generate xenogeneic organs. However, ethical issues prevent the study of human chimeras in the late embryonic stage of development. Primate embryonic stem cells (ESCs), which have similar pluripotency to ...

    journal_title：Protein & cell

    pub_type： 杂志文章

    doi：10.1007/s13238-019-00676-8

    authors： Fu R,Yu D,Ren J,Li C,Wang J,Feng G,Wang X,Wan H,Li T,Wang L,Zhang Y,Hai T,Li W,Zhou Q

    更新日期：2020-02-01 00:00:00

  • SNObase, a database for S-nitrosation modification.

    abstract：:S-Nitros(yl)ation is a ubiquitous redox-based post-translational modification of protein cysteine thiols by nitric oxide or its derivatives, which transduces the bioactivity of nitric oxide (NO) by regulation of protein conformation, activity, stability, localization and protein-protein interactions. These years, more...

    journal_title：Protein & cell

    pub_type： 杂志文章

    doi：10.1007/s13238-012-2094-6

    authors： Zhang X,Huang B,Zhang L,Zhang Y,Zhao Y,Guo X,Qiao X,Chen C

    更新日期：2012-12-01 00:00:00

  • The genetic and epigenetic alterations in human hepatocellular carcinoma: a recent update.

    abstract：:Hepatocellular carcinoma (HCC) is one of the most frequent human malignancies worldwide with very poor prognosis. It is generally accepted that the progression of HCC is a long-term process with accumulation of multiple genetic and epigenetic alterations, which further lead to the activation of critical oncogenes or i...

    journal_title：Protein & cell

    pub_type： 杂志文章,评审

    doi：10.1007/s13238-014-0065-9

    authors： Liu M,Jiang L,Guan XY

    更新日期：2014-09-01 00:00:00

  • Structural dynamics of the yeast Shwachman-Diamond syndrome protein (Sdo1) on the ribosome and its implication in the 60S subunit maturation.

    abstract：:The human Shwachman-Diamond syndrome (SDS) is an autosomal recessive disease caused by mutations in a highly conserved ribosome assembly factor SBDS. The functional role of SBDS is to cooperate with another assembly factor, elongation factor 1-like (Efl1), to promote the release of eukaryotic initiation factor 6 (eIF6...

    journal_title：Protein & cell

    pub_type： 杂志文章

    doi：10.1007/s13238-015-0242-5

    authors： Ma C,Yan K,Tan D,Li N,Zhang Y,Yuan Y,Li Z,Dong MQ,Lei J,Gao N

    更新日期：2016-03-01 00:00:00

  • T-cell receptor-engineered T cells for cancer treatment: current status and future directions.

    abstract：:T-cell receptor (TCR)-engineered T cells are a novel option for adoptive cell therapy used for the treatment of several advanced forms of cancer. Work using TCR-engineered T cells began more than two decades ago, with numerous preclinical studies showing that such cells could mediate tumor lysis and eradication. The s...

    journal_title：Protein & cell

    pub_type： 杂志文章,评审

    doi：10.1007/s13238-016-0367-1

    authors： Ping Y,Liu C,Zhang Y

    更新日期：2018-03-01 00:00:00

  • An examination of the OMIM database for associating mutation to a consensus reference sequence.

    abstract：:Gene mutation (e.g. substitution, insertion and deletion) and related phenotype information are important biomedical knowledge. Many biomedical databases (e.g. OMIM) incorporate such data. However, few studies have examined the quality of this data. In the current study, we examined the quality of protein single-point...

    journal_title：Protein & cell

    pub_type： 杂志文章

    doi：10.1007/s13238-012-2037-2

    authors： Li Z,Ying B,Liu X,Zhang X,Yu H

    更新日期：2012-03-01 00:00:00

  • POST1/C12ORF49 regulates the SREBP pathway by promoting site-1 protease maturation.

    abstract：:Sterol-regulatory element binding proteins (SREBPs) are the key transcriptional regulators of lipid metabolism. The activation of SREBP requires translocation of the SREBP precursor from the endoplasmic reticulum to the Golgi, where it is sequentially cleaved by site-1 protease (S1P) and site-2 protease and releases a...

    journal_title：Protein & cell

    pub_type： 杂志文章

    doi：10.1007/s13238-020-00753-3

    authors： Xiao J,Xiong Y,Yang LT,Wang JQ,Zhou ZM,Dong LW,Shi XJ,Zhao X,Luo J,Song BL

    更新日期：2020-07-14 00:00:00

  • Overexpression of sigma-1 receptor inhibits ADAM10 and ADAM17 mediated shedding in vitro.

    abstract：:The sigma-1 receptor is a molecular chaperone protein highly enriched in the brain. Recent studies linked it to many diseases, such as drug addition, Alzheimer's disease, stroke, depression, and even cancer. Sigma-1 receptor is enriched in lipid rafts, which are membrane microdomains essential in signaling processes. ...

    journal_title：Protein & cell

    pub_type： 杂志文章

    doi：10.1007/s13238-012-2006-9

    authors： Li J,Liu B,Gao X,Ma Z,CaoSong T,Mei YA,Zheng Y

    更新日期：2012-02-01 00:00:00

  • Molecular mechanisms for survival regulation of chronic myeloid leukemia stem cells.

    abstract：:Studies on chronic myeloid leukemia (CML) have served as a paradigm for cancer research and therapy. These studies involve the identification of the first cancer-associated chromosomal abnormality and the subsequent development of tyrosine kinase inhibitors (TKIs) that inhibit BCR-ABL kinase activity in CML. It become...

    journal_title：Protein & cell

    pub_type： 杂志文章,评审

    doi：10.1007/s13238-013-2115-0

    authors： Zhang H,Li S

    更新日期：2013-03-01 00:00:00

  • The role of Smad7 in oral mucositis.

    abstract：:Oral mucositis, a severe oral ulceration, is a common toxic effect of radio- or chemoradio-therapy and a limiting factor to using the maximum dose of radiation for effective cancer treatment. Among cancer patients, at least 40% and up to 70%, of individuals treated with standard chemotherapy regimens or upper-body rad...

    journal_title：Protein & cell

    pub_type： 杂志文章,评审

    doi：10.1007/s13238-014-0130-4

    authors： Bian L,Han G,Zhao CW,Garl PJ,Wang XJ

    更新日期：2015-03-01 00:00:00

  • Transmembrane domain dependent inhibitory function of FcγRIIB.

    abstract：:FcγRIIB, the only inhibitory IgG Fc receptor, functions to suppress the hyper-activation of immune cells. Numerous studies have illustrated its inhibitory function through the ITIM motif in the cytoplasmic tail of FcγRIIB. However, later studies revealed that in addition to the ITIM, the transmembrane (TM) domain of F...

    journal_title：Protein & cell

    pub_type： 杂志文章,评审

    doi：10.1007/s13238-018-0509-8

    authors： Wang J,Li Z,Xu L,Yang H,Liu W

    更新日期：2018-12-01 00:00:00

  • Proteomic and transcriptomic analysis of visual long-term memory in Drosophila melanogaster.

    abstract：:The fruit fly, Drosophila melanogaster, is able to discriminate visual landmarks and form visual long-term memory in a flight simulator. Studies focused on the molecular mechanism of long-term memory have shown that memory formation requires mRNA transcription and protein synthesis. However, little is known about the ...

    journal_title：Protein & cell

    pub_type： 杂志文章

    doi：10.1007/s13238-011-1019-0

    authors： Jiang H,Hou Q,Gong Z,Liu L

    更新日期：2011-03-01 00:00:00

  • Wld(S), Nmnats and axon degeneration--progress in the past two decades.

    abstract：:A chimeric protein called Wallerian degeneration slow (Wld(S)) was first discovered in a spontaneous mutant strain of mice that exhibited delayed Wallerian degeneration. This provides a useful tool in elucidating the mechanisms of axon degeneration. Over-expression of Wld(S) attenuates the axon degeneration that is as...

    journal_title：Protein & cell

    pub_type： 杂志文章,评审

    doi：10.1007/s13238-010-0021-2

    authors： Feng Y,Yan T,He Z,Zhai Q

    更新日期：2010-03-01 00:00:00

  • Mutation analysis of large tumor suppressor genes LATS1 and LATS2 supports a tumor suppressor role in human cancer.

    abstract：:In recent years, human cancer genome projects provide unprecedented opportunities for the discovery of cancer genes and signaling pathways that contribute to tumor development. While numerous gene mutations can be identified from each cancer genome, what these mutations mean for cancer is a challenging question to add...

    journal_title：Protein & cell

    pub_type： 杂志文章

    doi：10.1007/s13238-014-0122-4

    authors： Yu T,Bachman J,Lai ZC

    更新日期：2015-01-01 00:00:00

  • Structural and biochemical studies of RIG-I antiviral signaling.

    abstract：:Retinoic acid-inducible gene I (RIG-I) is an important pattern recognition receptor that detects viral RNA and triggers the production of type-I interferons through the downstream adaptor MAVS (also called IPS-1, CARDIF, or VISA). A series of structural studies have elaborated some of the mechanisms of dsRNA recogniti...

    journal_title：Protein & cell

    pub_type： 杂志文章

    doi：10.1007/s13238-012-2088-4

    authors： Feng M,Ding Z,Xu L,Kong L,Wang W,Jiao S,Shi Z,Greene MI,Cong Y,Zhou Z

    更新日期：2013-02-01 00:00:00

  • Phage display screening of therapeutic peptide for cancer targeting and therapy.

    abstract：:Recently, phage display technology has been announced as the recipient of Nobel Prize in Chemistry 2018. Phage display technique allows high affinity target-binding peptides to be selected from a complex mixture pool of billions of displayed peptides on phage in a combinatorial library and could be further enriched th...

    journal_title：Protein & cell

    pub_type： 杂志文章,评审

    doi：10.1007/s13238-019-0639-7

    authors： Saw PE,Song EW

    更新日期：2019-11-01 00:00:00

  • Mechanism involved in the modulation of photoreceptor-specific cyclic nucleotidegated channel by the tyrosine kinase adapter protein Grb14.

    abstract：:We recently found that growth factor receptor-bound (Grb) protein 14 is a novel physiological modulator of photoreceptor specific cyclic nucleotide-gated channel alpha subunit (CNGA1). Grb14 promotes the CNG channel closure through its Ras-associating (RA) domain. In the current study we show that this RA domain-media...

    journal_title：Protein & cell

    pub_type： 杂志文章

    doi：10.1007/s13238-011-1115-1

    authors： Gupta VK,Rajala A,Rodgers KK,Rajala RV

    更新日期：2011-11-01 00:00:00

  • How will telomeric complex be further contributed to our longevity? - the potential novel biomarkers of telomere complex counteracting both aging and cancer.

    abstract：:With the smooth move towards the coming expected clinical reports of anticancer pharmaceutical molecules targeting telomeres and telomerase, and also with the exciting success in the extension of lifespan by regulating telomerase activity without increased onset of oncogenesis in laboratory mouse models (Garcia-Cao et...

    journal_title：Protein & cell

    pub_type： 杂志文章,评审

    doi：10.1007/s13238-013-3002-4

    authors： Lu Y,Wei B,Zhang T,Chen Z,Ye J

    更新日期：2013-08-01 00:00:00