The protein quality control machinery regulates its misassembled proteasome subunits.

Abstract:

:Cellular toxicity introduced by protein misfolding threatens cell fitness and viability. Failure to eliminate these polypeptides is associated with various aggregation diseases. In eukaryotes, the ubiquitin proteasome system (UPS) plays a vital role in protein quality control (PQC), by selectively targeting misfolded proteins for degradation. While the assembly of the proteasome can be naturally impaired by many factors, the regulatory pathways that mediate the sorting and elimination of misassembled proteasomal subunits are poorly understood. Here, we reveal how the dysfunctional proteasome is controlled by the PQC machinery. We found that among the multilayered quality control mechanisms, UPS mediated degradation of its own misassembled subunits is the favored pathway. We also demonstrated that the Hsp42 chaperone mediates an alternative pathway, the accumulation of these subunits in cytoprotective compartments. Thus, we show that proteasome homeostasis is controlled through probing the level of proteasome assembly, and the interplay between UPS mediated degradation or their sorting into distinct cellular compartments.

journal_name

PLoS Genet

journal_title

PLoS genetics

authors

Peters LZ,Karmon O,David-Kadoch G,Hazan R,Yu T,Glickman MH,Ben-Aroya S

doi

10.1371/journal.pgen.1005178

subject

Has Abstract

pub_date

2015-04-28 00:00:00

pages

e1005178

issue

4

eissn

1553-7390

issn

1553-7404

pii

PGENETICS-D-14-01622

journal_volume

11

pub_type

杂志文章
  • Inhibition of GSK-3 ameliorates Abeta pathology in an adult-onset Drosophila model of Alzheimer's disease.

    abstract::Abeta peptide accumulation is thought to be the primary event in the pathogenesis of Alzheimer's disease (AD), with downstream neurotoxic effects including the hyperphosphorylation of tau protein. Glycogen synthase kinase-3 (GSK-3) is increasingly implicated as playing a pivotal role in this amyloid cascade. We have d...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1001087

    authors: Sofola O,Kerr F,Rogers I,Killick R,Augustin H,Gandy C,Allen MJ,Hardy J,Lovestone S,Partridge L

    更新日期:2010-09-02 00:00:00

  • The Non-coding Mammary Carcinoma Susceptibility Locus, Mcs5c, Regulates Pappa Expression via Age-Specific Chromatin Folding and Allele-Dependent DNA Methylation.

    abstract::In understanding the etiology of breast cancer, the contributions of both genetic and environmental risk factors are further complicated by the impact of breast developmental stage. Specifically, the time period ranging from childhood to young adulthood represents a critical developmental window in a woman's life when...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1006261

    authors: Henning AN,Haag JD,Smits BM,Gould MN

    更新日期:2016-08-18 00:00:00

  • Limiting of the innate immune response by SF3A-dependent control of MyD88 alternative mRNA splicing.

    abstract::Controlling infectious disease without inducing unwanted inflammatory disease requires proper regulation of the innate immune response. Thus, innate immunity needs to be activated when needed during an infection, but must be limited to prevent damage. To accomplish this, negative regulators of innate immunity limit th...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1003855

    authors: De Arras L,Alper S

    更新日期:2013-10-01 00:00:00

  • Inference of Candidate Germline Mutator Loci in Humans from Genome-Wide Haplotype Data.

    abstract::The rate of germline mutation varies widely between species but little is known about the extent of variation in the germline mutation rate between individuals of the same species. Here we demonstrate that an allele that increases the rate of germline mutation can result in a distinctive signature in the genomic regio...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1006549

    authors: Seoighe C,Scally A

    更新日期:2017-01-17 00:00:00

  • Cooperation, cis-interactions, versatility and evolutionary plasticity of multiple cis-acting elements underlie krox20 hindbrain regulation.

    abstract::Cis-regulation plays an essential role in the control of gene expression, and is particularly complex and poorly understood for developmental genes, which are subject to multiple levels of modulation. In this study, we performed a global analysis of the cis-acting elements involved in the control of the zebrafish deve...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1007581

    authors: Torbey P,Thierion E,Collombet S,de Cian A,Desmarquet-Trin-Dinh C,Dura M,Concordet JP,Charnay P,Gilardi-Hebenstreit P

    更新日期:2018-08-06 00:00:00

  • Dual functions of ASCIZ in the DNA base damage response and pulmonary organogenesis.

    abstract::Zn²(+)-finger proteins comprise one of the largest protein superfamilies with diverse biological functions. The ATM substrate Chk2-interacting Zn²(+)-finger protein (ASCIZ; also known as ATMIN and ZNF822) was originally linked to functions in the DNA base damage response and has also been proposed to be an essential c...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1001170

    authors: Jurado S,Smyth I,van Denderen B,Tenis N,Hammet A,Hewitt K,Ng JL,McNees CJ,Kozlov SV,Oka H,Kobayashi M,Conlan LA,Cole TJ,Yamamoto K,Taniguchi Y,Takeda S,Lavin MF,Heierhorst J

    更新日期:2010-10-21 00:00:00

  • Bacterial adaptation through loss of function.

    abstract::The metabolic capabilities and regulatory networks of bacteria have been optimized by evolution in response to selective pressures present in each species' native ecological niche. In a new environment, however, the same bacteria may grow poorly due to regulatory constraints or biochemical deficiencies. Adaptation to ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1003617

    authors: Hottes AK,Freddolino PL,Khare A,Donnell ZN,Liu JC,Tavazoie S

    更新日期:2013-01-01 00:00:00

  • Inter-homolog crossing-over and synapsis in Arabidopsis meiosis are dependent on the chromosome axis protein AtASY3.

    abstract::In this study we have analysed AtASY3, a coiled-coil domain protein that is required for normal meiosis in Arabidopsis. Analysis of an Atasy3-1 mutant reveals that loss of the protein compromises chromosome axis formation and results in reduced numbers of meiotic crossovers (COs). Although the frequency of DNA double-...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002507

    authors: Ferdous M,Higgins JD,Osman K,Lambing C,Roitinger E,Mechtler K,Armstrong SJ,Perry R,Pradillo M,Cuñado N,Franklin FC

    更新日期:2012-02-01 00:00:00

  • Rfx2 Stabilizes Foxj1 Binding at Chromatin Loops to Enable Multiciliated Cell Gene Expression.

    abstract::Cooperative transcription factor binding at cis-regulatory sites in the genome drives robust eukaryotic gene expression, and many such sites must be coordinated to produce coherent transcriptional programs. The transcriptional program leading to motile cilia formation requires members of the DNA-binding forkhead (Fox)...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1006538

    authors: Quigley IK,Kintner C

    更新日期:2017-01-19 00:00:00

  • Recruitment of the Ulp2 protease to the inner kinetochore prevents its hyper-sumoylation to ensure accurate chromosome segregation.

    abstract::The kinetochore is the central molecular machine that drives chromosome segregation in all eukaryotes. Genetic studies have suggested that protein sumoylation plays a role in regulating the inner kinetochore; however, the mechanism remains elusive. Here, we show that Saccharomyces cerevisiae Ulp2, an evolutionarily co...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008477

    authors: Suhandynata RT,Quan Y,Yang Y,Yuan WT,Albuquerque CP,Zhou H

    更新日期:2019-11-20 00:00:00

  • Multifaceted genome control by Set1 Dependent and Independent of H3K4 methylation and the Set1C/COMPASS complex.

    abstract::Histone modifiers are critical regulators of chromatin-based processes in eukaryotes. The histone methyltransferase Set1, a component of the Set1C/COMPASS complex, catalyzes the methylation at lysine 4 of histone H3 (H3K4me), a hallmark of euchromatin. Here, we show that the fission yeast Schizosaccharomyces pombe Set...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004740

    authors: Mikheyeva IV,Grady PJ,Tamburini FB,Lorenz DR,Cam HP

    更新日期:2014-10-30 00:00:00

  • Cytoneme-mediated signaling essential for tumorigenesis.

    abstract::Communication between neoplastic cells and cells of their microenvironment is critical to cancer progression. To investigate the role of cytoneme-mediated signaling as a mechanism for distributing growth factor signaling proteins between tumor and tumor-associated cells, we analyzed EGFR and RET Drosophila tumor model...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008415

    authors: Fereres S,Hatori R,Hatori M,Kornberg TB

    更新日期:2019-09-30 00:00:00

  • HSPB7 prevents cardiac conduction system defect through maintaining intercalated disc integrity.

    abstract::HSPB7 is a member of the small heat-shock protein (HSPB) family and is expressed in the cardiomyocytes from cardiogenesis onwards. A dramatic increase in HSPB7 is detected in the heart and blood plasma immediately after myocardial infarction. Additionally, several single-nucleotide polymorphisms of HSPB7 have been ide...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1006984

    authors: Liao WC,Juo LY,Shih YL,Chen YH,Yan YT

    更新日期:2017-08-21 00:00:00

  • Reverse GWAS: Using genetics to identify and model phenotypic subtypes.

    abstract::Recent and classical work has revealed biologically and medically significant subtypes in complex diseases and traits. However, relevant subtypes are often unknown, unmeasured, or actively debated, making automated statistical approaches to subtype definition valuable. We propose reverse GWAS (RGWAS) to identify and v...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008009

    authors: Dahl A,Cai N,Ko A,Laakso M,Pajukanta P,Flint J,Zaitlen N

    更新日期:2019-04-05 00:00:00

  • DNA damage as a consequence of NLR activation.

    abstract::DNA damage observed during plant immune responses is reported to be an intrinsic component of plant immunity. However, other immune responses may suppress DNA damage to maintain host genome integrity. Here, we show that immunity-related DNA damage can be abrogated by preventing cell death triggered by Nucleotide-bindi...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1007235

    authors: Rodriguez E,Chevalier J,El Ghoul H,Voldum-Clausen K,Mundy J,Petersen M

    更新日期:2018-02-20 00:00:00

  • Blimp1/Prdm1 Functions in Opposition to Irf1 to Maintain Neonatal Tolerance during Postnatal Intestinal Maturation.

    abstract::The neonatal intestine is a very complex and dynamic organ that must rapidly adapt and remodel in response to a barrage of environmental stimuli during the first few postnatal weeks. Recent studies demonstrate that the zinc finger transcriptional repressor Blimp1/Prdm1 plays an essential role governing postnatal repro...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1005375

    authors: Mould AW,Morgan MA,Nelson AC,Bikoff EK,Robertson EJ

    更新日期:2015-07-09 00:00:00

  • Correction: Methyl Farnesoate Plays a Dual Role in Regulating Drosophila Metamorphosis.

    abstract::[This corrects the article DOI: 10.1371/journal.pgen.1005038.]. ...

    journal_title:PLoS genetics

    pub_type: 已发布勘误

    doi:10.1371/journal.pgen.1006559

    authors: Wen D,Rivera-Perez C,Abdou M,Jia Q,He Q,Liu X,Zyaan O,Xu J,Bendena WG,Tobe SS,Noriega FG,Palli SR,Wang J,Li S

    更新日期:2017-01-20 00:00:00

  • BRCA1 and BRCA2 tumor suppressors in neural crest cells are essential for craniofacial bone development.

    abstract::Craniofacial abnormalities, including facial skeletal defects, comprise approximately one-third of all birth defects in humans. Since most bones in the face derive from cranial neural crest cells (CNCCs), which are multipotent stem cells, craniofacial bone disorders are largely attributed to defects in CNCCs. However,...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1007340

    authors: Kitami K,Kitami M,Kaku M,Wang B,Komatsu Y

    更新日期:2018-05-02 00:00:00

  • Physiological IRE-1-XBP-1 and PEK-1 signaling in Caenorhabditis elegans larval development and immunity.

    abstract::Endoplasmic reticulum (ER) stress activates the Unfolded Protein Response, a compensatory signaling response that is mediated by the IRE-1, PERK/PEK-1, and ATF-6 pathways in metazoans. Genetic studies have implicated roles for UPR signaling in animal development and disease, but the function of the UPR under physiolog...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002391

    authors: Richardson CE,Kinkel S,Kim DH

    更新日期:2011-11-01 00:00:00

  • A Novel Feedback Loop That Controls Bimodal Expression of Genetic Competence.

    abstract::Gene expression can be highly heterogeneous in isogenic cell populations. An extreme type of heterogeneity is the so-called bistable or bimodal expression, whereby a cell can differentiate into two alternative expression states. Stochastic fluctuations of protein levels, also referred to as noise, provide the necessar...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1005047

    authors: Gamba P,Jonker MJ,Hamoen LW

    更新日期:2015-06-25 00:00:00

  • Double-edged sword: The evolutionary consequences of the epigenetic silencing of transposable elements.

    abstract::Transposable elements (TEs) are genomic parasites that selfishly replicate at the expense of host fitness. Fifty years of evolutionary studies of TEs have concentrated on the deleterious genetic effects of TEs, such as their effects on disrupting genes and regulatory sequences. However, a flurry of recent work suggest...

    journal_title:PLoS genetics

    pub_type: 杂志文章,评审

    doi:10.1371/journal.pgen.1008872

    authors: Choi JY,Lee YCG

    更新日期:2020-07-16 00:00:00

  • Re-sequencing expands our understanding of the phenotypic impact of variants at GWAS loci.

    abstract::Genome-wide association studies (GWAS) have identified >500 common variants associated with quantitative metabolic traits, but in aggregate such variants explain at most 20-30% of the heritable component of population variation in these traits. To further investigate the impact of genotypic variation on metabolic trai...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004147

    authors: Service SK,Teslovich TM,Fuchsberger C,Ramensky V,Yajnik P,Koboldt DC,Larson DE,Zhang Q,Lin L,Welch R,Ding L,McLellan MD,O'Laughlin M,Fronick C,Fulton LL,Magrini V,Swift A,Elliott P,Jarvelin MR,Kaakinen M,McCarthy

    更新日期:2014-01-30 00:00:00

  • Genome-wide analysis of KAP1 binding suggests autoregulation of KRAB-ZNFs.

    abstract::We performed a genome-scale chromatin immunoprecipitation (ChIP)-chip comparison of two modifications (trimethylation of lysine 9 [H3me3K9] and trimethylation of lysine 27 [H3me3K27]) of histone H3 in Ntera2 testicular carcinoma cells and in three different anatomical sources of primary human fibroblasts. We found tha...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.0030089

    authors: O'Geen H,Squazzo SL,Iyengar S,Blahnik K,Rinn JL,Chang HY,Green R,Farnham PJ

    更新日期:2007-06-01 00:00:00

  • Loss of hepatocyte cell division leads to liver inflammation and fibrosis.

    abstract::The liver possesses a remarkable regenerative capacity based partly on the ability of hepatocytes to re-enter the cell cycle and divide to replace damaged cells. This capability is substantially reduced upon chronic damage, but it is not clear if this is a cause or consequence of liver disease. Here, we investigate wh...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1009084

    authors: Dewhurst MR,Ow JR,Zafer G,van Hul NKM,Wollmann H,Bisteau X,Brough D,Choi H,Kaldis P

    更新日期:2020-11-04 00:00:00

  • Systems biology of tissue-specific response to Anaplasma phagocytophilum reveals differentiated apoptosis in the tick vector Ixodes scapularis.

    abstract::Anaplasma phagocytophilum is an emerging pathogen that causes human granulocytic anaplasmosis. Infection with this zoonotic pathogen affects cell function in both vertebrate host and the tick vector, Ixodes scapularis. Global tissue-specific response and apoptosis signaling pathways were characterized in I. scapularis...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1005120

    authors: Ayllón N,Villar M,Galindo RC,Kocan KM,Šíma R,López JA,Vázquez J,Alberdi P,Cabezas-Cruz A,Kopáček P,de la Fuente J

    更新日期:2015-03-27 00:00:00

  • Cuba: exploring the history of admixture and the genetic basis of pigmentation using autosomal and uniparental markers.

    abstract::We carried out an admixture analysis of a sample comprising 1,019 individuals from all the provinces of Cuba. We used a panel of 128 autosomal Ancestry Informative Markers (AIMs) to estimate the admixture proportions. We also characterized a number of haplogroup diagnostic markers in the mtDNA and Y-chromosome in orde...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004488

    authors: Marcheco-Teruel B,Parra EJ,Fuentes-Smith E,Salas A,Buttenschøn HN,Demontis D,Torres-Español M,Marín-Padrón LC,Gómez-Cabezas EJ,Alvarez-Iglesias V,Mosquera-Miguel A,Martínez-Fuentes A,Carracedo A,Børglum AD,Mors O

    更新日期:2014-07-24 00:00:00

  • PAX6 regulates melanogenesis in the retinal pigmented epithelium through feed-forward regulatory interactions with MITF.

    abstract::During organogenesis, PAX6 is required for establishment of various progenitor subtypes within the central nervous system, eye and pancreas. PAX6 expression is maintained in a variety of cell types within each organ, although its role in each lineage and how it acquires cell-specific activity remain elusive. Herein, w...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004360

    authors: Raviv S,Bharti K,Rencus-Lazar S,Cohen-Tayar Y,Schyr R,Evantal N,Meshorer E,Zilberberg A,Idelson M,Reubinoff B,Grebe R,Rosin-Arbesfeld R,Lauderdale J,Lutty G,Arnheiter H,Ashery-Padan R

    更新日期:2014-05-29 00:00:00

  • A cis-regulatory signature for chordate anterior neuroectodermal genes.

    abstract::One of the striking findings of comparative developmental genetics was that expression patterns of core transcription factors are extraordinarily conserved in bilaterians. However, it remains unclear whether cis-regulatory elements of their target genes also exhibit common signatures associated with conserved embryoni...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000912

    authors: Haeussler M,Jaszczyszyn Y,Christiaen L,Joly JS

    更新日期:2010-04-15 00:00:00

  • Correction: The Epigenomic Landscape of Prokaryotes.

    abstract::[This corrects the article DOI: 10.1371/journal.pgen.1005854.]. ...

    journal_title:PLoS genetics

    pub_type: 已发布勘误

    doi:10.1371/journal.pgen.1006064

    authors: PLOS Genetics Staff.

    更新日期:2016-05-12 00:00:00

  • Correction: Pleiotropic Mechanisms Indicated for Sex Differences in Autism.

    abstract::[This corrects the article DOI: 10.1371/journal.pgen.1006425.]. ...

    journal_title:PLoS genetics

    pub_type: 杂志文章,已发布勘误

    doi:10.1371/journal.pgen.1006831

    authors: Mitra I,Tsang K,Ladd-Acosta C,Croen LA,Aldinger KA,Hendren RL,Traglia M,Lavillaureix A,Zaitlen N,Oldham MC,Levitt P,Nelson S,Amaral DG,Hertz-Picciotto I,Fallin MD,Weiss LA

    更新日期:2017-06-07 00:00:00