Exposure of bipartite hydrophobic signal triggers nuclear quality control of Ndc10 at the endoplasmic reticulum/nuclear envelope.

Abstract:

:Proper functioning of the protein-folding quality control network depends on the network's ability to discern diverse structural perturbations to the native states of its protein substrates. Despite the centrality of the detection of misfolded states to cell home-ostasis, very little is known about the exact sequence and structural features that mark a protein as being misfolded. To investigate these features, we studied the requirements for the degradation of the yeast kinetochore protein Ndc10p. Mutant Ndc10p is a substrate of a protein-folding quality control pathway mediated by the E3 ubiquitin (Ub) ligase Doa10p at the endoplasmic reticulum (ER)/nuclear envelope membrane. Analysis of Ndc10p mutant derivatives, employing a reverse genetics approach, identified an autonomous quality control-associated degradation motif near the C-terminus of the protein. This motif is composed of two indispensable hydrophobic elements: a hydrophobic surface of an amphipathic helix and a loosely structured hydrophobic C-terminal tail. Site-specific point mutations expose these elements, triggering ubiquitin-mediated and HSP70 chaperone-dependent degradation of Ndc10p. These findings substantiate the ability of the ER quality control system to recognize subtle perturbation(s) in the native structure of a nuclear protein.

journal_name

Mol Biol Cell

authors

Furth N,Gertman O,Shiber A,Alfassy OS,Cohen I,Rosenberg MM,Doron NK,Friedler A,Ravid T

doi

10.1091/mbc.E11-05-0463

subject

Has Abstract

pub_date

2011-12-01 00:00:00

pages

4726-39

issue

24

eissn

1059-1524

issn

1939-4586

pii

mbc.E11-05-0463

journal_volume

22

pub_type

杂志文章
  • Cell cycle-dependent changes in microtubule dynamics in living cells expressing green fluorescent protein-alpha tubulin.

    abstract::LLCPK-1 cells were transfected with a green fluorescent protein (GFP)-alpha tubulin construct and a cell line permanently expressing GFP-alpha tubulin was established (LLCPK-1alpha). The mitotic index and doubling time for LLCPK-1alpha were not significantly different from parental cells. Quantitative immunoblotting s...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.12.4.971

    authors: Rusan NM,Fagerstrom CJ,Yvon AM,Wadsworth P

    更新日期:2001-04-01 00:00:00

  • Biogenesis of N-cadherin-dependent cell-cell contacts in living fibroblasts is a microtubule-dependent kinesin-driven mechanism.

    abstract::Cadherin-mediated cell-cell adhesion is a dynamic process that is regulated during embryonic development, cell migration, and differentiation. Different cadherins are expressed in specific tissues consistent with their roles in cell type recognition. In this study, we examine the formation of N-cadherin-dependent cell...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.01-07-0337

    authors: Mary S,Charrasse S,Meriane M,Comunale F,Travo P,Blangy A,Gauthier-Rouvière C

    更新日期:2002-01-01 00:00:00

  • Superresolution microscopy of the β-carboxysome reveals a homogeneous matrix.

    abstract::Carbon fixation in cyanobacteria makes a major contribution to the global carbon cycle. The cyanobacterial carboxysome is a proteinaceous microcompartment that protects and concentrates the carbon-fixing enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) in a paracrystalline lattice, making it possible f...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E17-01-0069

    authors: Niederhuber MJ,Lambert TJ,Yapp C,Silver PA,Polka JK

    更新日期:2017-10-01 00:00:00

  • Novel function of clathrin light chain in promoting endocytic vesicle formation.

    abstract::Clathrin-mediated endocytosis is a major pathway for uptake of lipid and protein cargo at the plasma membrane. The lattices of clathrin-coated pits and vesicles are comprised of triskelions, each consisting of three oligomerized heavy chains (HC) bound by a light chain (LC). In addition to binding HC, LC interacts wit...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e06-07-0606

    authors: Newpher TM,Idrissi FZ,Geli MI,Lemmon SK

    更新日期:2006-10-01 00:00:00

  • Fission yeast Ste9, a homolog of Hct1/Cdh1 and Fizzy-related, is a novel negative regulator of cell cycle progression during G1-phase.

    abstract::When proliferating fission yeast cells are exposed to nitrogen starvation, they initiate conjugation and differentiate into ascospores. Cell cycle arrest in the G1-phase is one of the prerequisites for cell differentiation, because conjugation occurs only in the pre-Start G1-phase. The role of ste9(+) in the cell cycl...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.9.5.1065

    authors: Kitamura K,Maekawa H,Shimoda C

    更新日期:1998-05-01 00:00:00

  • Yeast vacuolar HOPS, regulated by its kinase, exploits affinities for acidic lipids and Rab:GTP for membrane binding and to catalyze tethering and fusion.

    abstract::Fusion of yeast vacuoles requires the Rab GTPase Ypt7p, four SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors), the SNARE disassembly chaperones Sec17p/Sec18p, vacuolar lipids, and the Rab-effector complex HOPS (homotypic fusion and vacuole protein sorting). Two HOPS subunits have direct ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E14-08-1298

    authors: Orr A,Wickner W,Rusin SF,Kettenbach AN,Zick M

    更新日期:2015-01-15 00:00:00

  • Expression of a major surface protein of Trypanosoma brucei insect forms is controlled by the activity of mitochondrial enzymes.

    abstract::In cycling between the mammalian host and the tsetse fly vector, trypanosomes undergo major changes in energy metabolism and surface coat composition. Early procyclic (insect) forms in the tsetse fly midgut are coated by glycoproteins known as EP and GPEET procyclins. EP expression continues in late procyclic forms, w...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-04-0341

    authors: Vassella E,Probst M,Schneider A,Studer E,Renggli CK,Roditi I

    更新日期:2004-09-01 00:00:00

  • Intracellular transport, assembly, and degradation of wild-type and disease-linked mutant gap junction proteins.

    abstract::More than 130 different mutations in the gap junction integral plasma membrane protein connexin32 (Cx32) have been linked to the human peripheral neuropathy X-linked Charcot-Marie-Tooth disease (CMTX). How these various mutants are processed by the cell and the mechanism(s) by which they cause CMTX are unknown. To add...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.11.6.1933

    authors: VanSlyke JK,Deschenes SM,Musil LS

    更新日期:2000-06-01 00:00:00

  • p120-catenin and β-catenin differentially regulate cadherin adhesive function.

    abstract::Vascular endothelial (VE)-cadherin, the major adherens junction adhesion molecule in endothelial cells, interacts with p120-catenin and β-catenin through its cytoplasmic tail. However, the specific functional contributions of the catenins to the establishment of strong adhesion are not fully understood. Here we use bi...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E12-06-0471

    authors: Oas RG,Nanes BA,Esimai CC,Vincent PA,García AJ,Kowalczyk AP

    更新日期:2013-03-01 00:00:00

  • Degradation of stearoyl-coenzyme A desaturase: endoproteolytic cleavage by an integral membrane protease.

    abstract::Stearoyl-coenzyme A desaturase (SCD) is a key regulator of membrane fluidity, turns over rapidly, and represents a prototype for selective degradation of resident proteins of the endoplasmic reticulum. Using detergent-solubilized, desaturase-induced rat liver microsomes we have characterized a protease that degrades S...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.9.12.3445

    authors: Heinemann FS,Ozols J

    更新日期:1998-12-01 00:00:00

  • Sequential actions of myotubularin lipid phosphatases regulate endosomal PI(3)P and growth factor receptor trafficking.

    abstract::Two different human diseases, X-linked myotubular myopathy and Charcot-Marie-Tooth disease, result from mutant MTM1 or MTMR2 lipid phosphatases. Although events involved in endosomal PI(3)P and PI(3,5)P(2) synthesis are well established and pivotal in receptor signaling and degradation, enzymes involved in phosphoinos...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e08-04-0367

    authors: Cao C,Backer JM,Laporte J,Bedrick EJ,Wandinger-Ness A

    更新日期:2008-08-01 00:00:00

  • Modulation of myoblast fusion by caveolin-3 in dystrophic skeletal muscle cells: implications for Duchenne muscular dystrophy and limb-girdle muscular dystrophy-1C.

    abstract::Caveolae are vesicular invaginations of the plasma membrane. Caveolin-3 is the principal structural component of caveolae in skeletal muscle cells in vivo. We have recently generated caveolin-3 transgenic mice and demonstrated that overexpression of wild-type caveolin-3 in skeletal muscle fibers is sufficient to induc...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e03-03-0161

    authors: Volonte D,Peoples AJ,Galbiati F

    更新日期:2003-10-01 00:00:00

  • A novel transcriptional enhancer is involved in the prolactin- and extracellular matrix-dependent regulation of beta-casein gene expression.

    abstract::Lactogenic hormones and extracellular matrix (ECM) act synergistically to regulate beta-casein expression in culture. We have developed a functional subpopulation of the mouse mammary epithelial cell strain COMMA-1D (designated CID 9), which expresses high level of beta-casein, forms alveolar-like structures when plat...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.3.6.699

    authors: Schmidhauser C,Casperson GF,Myers CA,Sanzo KT,Bolten S,Bissell MJ

    更新日期:1992-06-01 00:00:00

  • Functional analysis and importance for host cell infection of the Ca2+-conducting subunits of the mitochondrial calcium uniporter of Trypanosoma cruzi.

    abstract::We report here that Trypanosoma cruzi, the etiologic agent of Chagas disease, possesses two unique paralogues of the mitochondrial calcium uniporter complex TcMCU subunit that we named TcMCUc and TcMCUd. The predicted structure of the proteins indicates that, as predicted for the TcMCU and TcMCUb paralogues, they are ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E19-03-0152

    authors: Chiurillo MA,Lander N,Bertolini MS,Vercesi AE,Docampo R

    更新日期:2019-07-01 00:00:00

  • Quantitative analysis of APP axonal transport in neurons: role of JIP1 in enhanced APP anterograde transport.

    abstract::Alzheimer's β-amyloid precursor protein (APP) associates with kinesin-1 via JNK-interacting protein 1 (JIP1); however, the role of JIP1 in APP transport by kinesin-1 in neurons remains unclear. We performed a quantitative analysis to understand the role of JIP1 in APP axonal transport. In JIP1-deficient neurons, we fi...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E14-06-1111

    authors: Chiba K,Araseki M,Nozawa K,Furukori K,Araki Y,Matsushima T,Nakaya T,Hata S,Saito Y,Uchida S,Okada Y,Nairn AC,Davis RJ,Yamamoto T,Kinjo M,Taru H,Suzuki T

    更新日期:2014-11-05 00:00:00

  • Actin-binding protein G (AbpG) participates in modulating the actin cytoskeleton and cell migration in Dictyostelium discoideum.

    abstract::Cell migration is involved in various physiological and pathogenic events, and the complex underlying molecular mechanisms have not been fully elucidated. The simple eukaryote Dictyostelium discoideum displays chemotactic locomotion in stages of its life cycle. By characterizing a Dictyostelium mutant defective in che...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E14-05-0972

    authors: Lin WC,Wang LC,Pang TL,Chen MY

    更新日期:2015-03-15 00:00:00

  • Distinct functions for Arf guanine nucleotide exchange factors at the Golgi complex: GBF1 and BIGs are required for assembly and maintenance of the Golgi stack and trans-Golgi network, respectively.

    abstract::We examined the relative function of the two classes of guanine nucleotide exchange factors (GEFs) for ADP-ribosylation factors that regulate recruitment of coat proteins on the Golgi complex. Complementary overexpression and RNA-based knockdown approaches established that GBF1 regulates COPI recruitment on cis-Golgi ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e07-04-0394

    authors: Manolea F,Claude A,Chun J,Rosas J,Melançon P

    更新日期:2008-02-01 00:00:00

  • An Lsm2-Lsm7 complex in Saccharomyces cerevisiae associates with the small nucleolar RNA snR5.

    abstract::Sm-like (Lsm) proteins function in a variety of RNA-processing events. In yeast, the Lsm2-Lsm8 complex binds and stabilizes the spliceosomal U6 snRNA, whereas the Lsm1-Lsm7 complex functions in mRNA decay. Here we report that a third Lsm complex, consisting of Lsm2-Lsm7 proteins, associates with snR5, a box H/ACA snoR...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-02-0116

    authors: Fernandez CF,Pannone BK,Chen X,Fuchs G,Wolin SL

    更新日期:2004-06-01 00:00:00

  • Heterogeneous nuclear ribonucleoprotein A2 is a common transcriptional coactivator in the nuclear transcription response to mitochondrial respiratory stress.

    abstract::Mitochondrial dysfunction and altered transmembrane potential initiate a mitochondrial respiratory stress response, also known as mitochondrial retrograde response, in a wide spectrum of cells. The mitochondrial stress response activates calcineurin, which regulates transcription factors, including a new nuclear facto...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e09-04-0296

    authors: Guha M,Pan H,Fang JK,Avadhani NG

    更新日期:2009-09-01 00:00:00

  • EB1 is essential during Drosophila development and plays a crucial role in the integrity of chordotonal mechanosensory organs.

    abstract::EB1 is a conserved microtubule plus end tracking protein considered to play crucial roles in microtubule organization and the interaction of microtubules with the cell cortex. Despite intense studies carried out in yeast and cultured cells, the role of EB1 in multicellular systems remains to be elucidated. Here, we de...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-07-0633

    authors: Elliott SL,Cullen CF,Wrobel N,Kernan MJ,Ohkura H

    更新日期:2005-02-01 00:00:00

  • Measuring fast gene dynamics in single cells with time-lapse luminescence microscopy.

    abstract::Time-lapse fluorescence microscopy is an important tool for measuring in vivo gene dynamics in single cells. However, fluorescent proteins are limited by slow chromophore maturation times and the cellular autofluorescence or phototoxicity that arises from light excitation. An alternative is luciferase, an enzyme that ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E14-07-1187

    authors: Mazo-Vargas A,Park H,Aydin M,Buchler NE

    更新日期:2014-11-05 00:00:00

  • Epsilon-tubulin is an essential component of the centriole.

    abstract::Centrioles and basal bodies are cylinders composed of nine triplet microtubule blades that play essential roles in the centrosome and in flagellar assembly. Chlamydomonas cells with the bld2-1 mutation fail to assemble doublet and triplet microtubules and have defects in cleavage furrow placement and meiosis. Using po...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e02-04-0205

    authors: Dutcher SK,Morrissette NS,Preble AM,Rackley C,Stanga J

    更新日期:2002-11-01 00:00:00

  • The Ndc80 complex uses a tripartite attachment point to couple microtubule depolymerization to chromosome movement.

    abstract::In kinetochores, the Ndc80 complex couples the energy in a depolymerizing microtubule to perform the work of moving chromosomes. The complex directly binds microtubules using an unstructured, positively charged N-terminal tail located on Hec1/Ndc80. Hec1/Ndc80 also contains a calponin homology domain (CHD) that increa...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E10-07-0626

    authors: Tooley JG,Miller SA,Stukenberg PT

    更新日期:2011-04-15 00:00:00

  • Chironomus tentans-repressor splicing factor represses SR protein function locally on pre-mRNA exons and is displaced at correct splice sites.

    abstract::Chironomus tentans-repressor splicing factor (Ct-RSF) represses the activation of splicing by SR proteins in vitro. Ct-RSF colocalizes with the Ser-Arg-rich (SR) protein hrp45 in interchromatin granule clusters and coimmunoprecipitates with hrp45 in nuclear extracts. Ct-RSF and hrp45 can also interact directly in vitr...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e05-04-0339

    authors: Björk P,Wetterberg-Strandh I,Baurén G,Wieslander L

    更新日期:2006-01-01 00:00:00

  • Phosphorylation of Rab11-FIP2 regulates polarity in MDCK cells.

    abstract::The Rab11 effector Rab11-family interacting protein 2 (Rab11-FIP2) regulates transcytosis through its interactions with Rab11a and myosin Vb. Previous studies implicated Rab11-FIP2 in the establishment of polarity in Madin-Darby canine kidney (MDCK) cells through phosphorylation of Ser-227 by MARK2. Here we examine th...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E11-08-0681

    authors: Lapierre LA,Avant KM,Caldwell CM,Oztan A,Apodaca G,Knowles BC,Roland JT,Ducharme NA,Goldenring JR

    更新日期:2012-06-01 00:00:00

  • RNA polymerase III in Cajal bodies and lampbrush chromosomes of the Xenopus oocyte nucleus.

    abstract::We used immunofluorescence to study the distribution and targeting of RNA polymerase (pol) III subunits and pol III transcription factors in the Xenopus laevis oocyte nucleus. Antibodies against several of these proteins stained Cajal bodies and approximately 90 specific sites on the lampbrush chromosomes. Some of the...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e02-05-0281

    authors: Murphy C,Wang Z,Roeder RG,Gall JG

    更新日期:2002-10-01 00:00:00

  • Deletion of nudC, a nuclear migration gene of Aspergillus nidulans, causes morphological and cell wall abnormalities and is lethal.

    abstract::Nuclear migration is required for normal development in both higher and lower eukaryotes. In fungi this process is mediated by cytoplasmic dynein. It is believed that this motor protein is anchored to the cell membrane and moves nuclei by capturing and pulling on spindle pole body microtubules. To date, four genes hav...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.8.9.1735

    authors: Chiu YH,Xiang X,Dawe AL,Morris NR

    更新日期:1997-09-01 00:00:00

  • Apoptosome-deficient cells lose cytochrome c through proteasomal degradation but survive by autophagy-dependent glycolysis.

    abstract::Cytochrome c release from mitochondria promotes apoptosome formation and caspase activation. The question as to whether mitochondrial permeabilization kills cells via a caspase-independent pathway when caspase activation is prevented is still open. Here we report that proneural cells of embryonic origin, when induced ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e07-09-0858

    authors: Ferraro E,Pulicati A,Cencioni MT,Cozzolino M,Navoni F,di Martino S,Nardacci R,Carrì MT,Cecconi F

    更新日期:2008-08-01 00:00:00

  • Drosophila Wee1 kinase rescues fission yeast from mitotic catastrophe and phosphorylates Drosophila Cdc2 in vitro.

    abstract::Cdc2 kinase activity is required for triggering entry into mitosis in all known eukaryotes. Elaborate mechanisms have evolved for regulating Cdc2 activity so that mitosis occurs in a timely manner, when preparations for its execution are complete. In Schizosaccharomyces pombe, Wee1 and a related Mik1 kinase are Cdc2-i...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.6.10.1333

    authors: Campbell SD,Sprenger F,Edgar BA,O'Farrell PH

    更新日期:1995-10-01 00:00:00

  • Condensin suppresses recombination and regulates double-strand break processing at the repetitive ribosomal DNA array to ensure proper chromosome segregation during meiosis in budding yeast.

    abstract::During meiosis, homologues are linked by crossover, which is required for bipolar chromosome orientation before chromosome segregation at anaphase I. The repetitive ribosomal DNA (rDNA) array, however, undergoes little or no meiotic recombination. Hyperrecombination can cause chromosome missegregation and rDNA copy nu...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E14-05-0957

    authors: Li P,Jin H,Yu HG

    更新日期:2014-10-01 00:00:00