Dosage compensation plans: protein aggregation provides additional insurance against aneuploidy.

Abstract:

:Gene dosage alterations caused by aneuploidy are a common feature of most cancers yet pose severe proteotoxic challenges. Therefore, cells have evolved various dosage compensation mechanisms to limit the damage caused by the ensuing protein level imbalances. For instance, for heteromeric protein complexes, excess nonstoichiometric subunits are rapidly recognized and degraded. In this issue of Genes & Development, Brennan et al. (pp. 1031-1047) reveal that sequestration of nonstoichiometric subunits into aggregates is an alternative mechanism for dosage compensation in aneuploid budding yeast and human cell lines. Using a combination of proteomic and genetic techniques, they found that excess proteins undergo either degradation or aggregation but not both. Which route is preferred depends on the half-life of the protein in question. Given the multitude of diseases linked to either aneuploidy or protein aggregation, this study could serve as a springboard for future studies with broad-spanning implications.

journal_name

Genes Dev

journal_title

Genes & development

authors

Samant RS,Masto VB,Frydman J

doi

10.1101/gad.329383.119

subject

Has Abstract

pub_date

2019-08-01 00:00:00

pages

1027-1030

issue

15-16

eissn

0890-9369

issn

1549-5477

pii

33/15-16/1027

journal_volume

33

pub_type

评论
  • Runx1 prevents wasting, myofibrillar disorganization, and autophagy of skeletal muscle.

    abstract::Disruptions in the use of skeletal muscle lead to muscle atrophy. After short periods of disuse, muscle atrophy is reversible, and even after prolonged periods of inactivity, myofiber degeneration is uncommon. The pathways that regulate atrophy, initiated either by peripheral nerve damage, immobilization, aging, catab...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1318305

    authors: Wang X,Blagden C,Fan J,Nowak SJ,Taniuchi I,Littman DR,Burden SJ

    更新日期:2005-07-15 00:00:00

  • Half helical turn spacing changes convert a frog into a mouse rDNA promoter: a distant upstream domain determines the helix face of the initiation site.

    abstract::Transcription of frog rDNA by mouse cell factors is the only documented exception to the observed species selectivity of rRNA gene expression. This heterologous transcription is authentic in that it uses the normal frog upstream and core promoter domains, as well as the normal mouse polymerase I transcription factors,...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.4.1.52

    authors: Pape LK,Windle JJ,Sollner-Webb B

    更新日期:1990-01-01 00:00:00

  • Differentiation-induced gene expression in 3T3-L1 preadipocytes: CCAAT/enhancer binding protein interacts with and activates the promoters of two adipocyte-specific genes.

    abstract::Previous studies have shown that differentiation of 3T3-L1 preadipocytes leads to the transcriptional activation of a group of adipose-specific genes. As an approach to defining the mechanism responsible for activating the expression of these genes, we investigated the binding of nuclear factors to the promoters of tw...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.3.9.1323

    authors: Christy RJ,Yang VW,Ntambi JM,Geiman DE,Landschulz WH,Friedman AD,Nakabeppu Y,Kelly TJ,Lane MD

    更新日期:1989-09-01 00:00:00

  • Myc family oncoproteins function through a common pathway to transform normal cells in culture: cross-interference by Max and trans-acting dominant mutants.

    abstract::The myc family of cellular oncogenes encodes three highly related nuclear phosphoproteins (c-Myc, N-Myc, and L-Myc) that are believed to function as sequence-specific transcription factors capable of regulating genes important in cellular growth and differentiation. Current evidence indicates that Myc family proteins ...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.6.8.1480

    authors: Mukherjee B,Morgenbesser SD,DePinho RA

    更新日期:1992-08-01 00:00:00

  • Deficient mismatch repair improves organismal fitness and survival of mice with dysfunctional telomeres.

    abstract::Mismatch repair (MMR) has important roles in meiotic and mitotic recombination, DNA damage signaling, and various aspects of DNA metabolism including class-switch recombination, somatic hypermutation, and triplet-repeat expansion. Defects in MMR are responsible for human cancers characterized by microsatellite instabi...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.430107

    authors: Siegl-Cachedenier I,Muñoz P,Flores JM,Klatt P,Blasco MA

    更新日期:2007-09-01 00:00:00

  • Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities.

    abstract::Although progesterone has been recognized as essential for the establishment and maintenance of pregnancy, this steroid hormone has been recently implicated to have a functional role in a number of other reproductive events. The physiological effects of progesterone are mediated by the progesterone receptor (PR), a me...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.9.18.2266

    authors: Lydon JP,DeMayo FJ,Funk CR,Mani SK,Hughes AR,Montgomery CA Jr,Shyamala G,Conneely OM,O'Malley BW

    更新日期:1995-09-15 00:00:00

  • A physiological role for gene loops in yeast.

    abstract::DNA loops that juxtapose the promoter and terminator regions of RNA polymerase II-transcribed genes have been identified in yeast and mammalian cells. Loop formation is transcription-dependent and requires components of the pre-mRNA 3'-end processing machinery. Here we report that looping at the yeast GAL10 gene persi...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1823609

    authors: Lainé JP,Singh BN,Krishnamurthy S,Hampsey M

    更新日期:2009-11-15 00:00:00

  • Suprabasal expression of a dominant-negative RXR alpha mutant in transgenic mouse epidermis impairs regulation of gene transcription and basal keratinocyte proliferation by RAR-selective retinoids.

    abstract::To determine whether 9-cis retinoic acid receptors (RXRs) regulate the biological activity of all-trans retinoic acid (tRA) and its receptors (RARs) in skin, we have targeted a dominant-negative RXR alpha (dnRXR alpha) lacking transactivation function AF-2 to differentiated suprabasal keratinocytes in the epidermis of...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.11.1.59

    authors: Feng X,Peng ZH,Di W,Li XY,Rochette-Egly C,Chambon P,Voorhees JJ,Xiao JH

    更新日期:1997-01-01 00:00:00

  • Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration.

    abstract::Although Apc is well characterized as a tumor-suppressor gene in the intestine, the precise mechanism of this suppression remains to be defined. Using a novel inducible Ahcre transgenic line in conjunction with a loxP-flanked Apc allele we, show that loss of Apc acutely activates Wnt signaling through the nuclear accu...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.287404

    authors: Sansom OJ,Reed KR,Hayes AJ,Ireland H,Brinkmann H,Newton IP,Batlle E,Simon-Assmann P,Clevers H,Nathke IS,Clarke AR,Winton DJ

    更新日期:2004-06-15 00:00:00

  • The helix-loop-helix protein Id-2 enhances cell proliferation and binds to the retinoblastoma protein.

    abstract::Cell growth and differentiation are usually antagonistic. Proteins of the basic helix-loop-helix (bHLH) family bind DNA and play important roles in the differentiation of specific cell types. Id proteins heterodimerize with bHLH transcription factors, blocking their activation of lineage-specific gene expression and t...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.8.11.1270

    authors: Iavarone A,Garg P,Lasorella A,Hsu J,Israel MA

    更新日期:1994-06-01 00:00:00

  • Termination-altering amino acid substitutions in the beta' subunit of Escherichia coli RNA polymerase identify regions involved in RNA chain elongation.

    abstract::To identify regions of the largest subunit of RNA polymerase that are potentially involved in transcript elongation and termination, we have characterized amino acid substitutions in the beta' subunit of Escherichia coli RNA polymerase that alter expression of reporter genes preceded by terminators in vivo. Terminatio...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.8.23.2913

    authors: Weilbaecher R,Hebron C,Feng G,Landick R

    更新日期:1994-12-01 00:00:00

  • RNAi is activated during Drosophila oocyte maturation in a manner dependent on aubergine and spindle-E.

    abstract::Gene silencing by double-stranded RNA is a widespread phenomenon called RNAi, involving homology-dependent degradation of mRNAs. Here we show that RNAi is established in the Drosophila female germ line. mRNA transcripts are translationally quiescent at the arrested oocyte stage and are insensitive to RNAi. Upon oocyte...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.990802

    authors: Kennerdell JR,Yamaguchi S,Carthew RW

    更新日期:2002-08-01 00:00:00

  • A master CLOCK hard at work brings rhythm to the transcriptome.

    abstract::In this issue of Genes & Development, Abruzzi et al. (pp. 2374-2386) use chromatin immunoprecipitation (ChIP) tiling array assays (ChIP-chip) to show that physical interactions between circadian (≅24-h) clock machineries and genomes are more widespread than previously thought and provide novel insights into how clocks...

    journal_title:Genes & development

    pub_type: 评论,杂志文章

    doi:10.1101/gad.180984.111

    authors: Edery I

    更新日期:2011-11-15 00:00:00

  • Imp2 controls oxidative phosphorylation and is crucial for preserving glioblastoma cancer stem cells.

    abstract::Growth of numerous cancer types is believed to be driven by a subpopulation of poorly differentiated cells, often referred to as cancer stem cells (CSCs), that have the capacity for self-renewal, tumor initiation, and generation of nontumorigenic progeny. Despite their potentially key role in tumor establishment and m...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.188292.112

    authors: Janiszewska M,Suvà ML,Riggi N,Houtkooper RH,Auwerx J,Clément-Schatlo V,Radovanovic I,Rheinbay E,Provero P,Stamenkovic I

    更新日期:2012-09-01 00:00:00

  • Chk2/hCds1 functions as a DNA damage checkpoint in G(1) by stabilizing p53.

    abstract::Chk2/hcds1, the human homolog of the Saccharomyces cerevisiae RAD53/SPK1 and Schizosaccharomyces pombe cds1 DNA damage checkpoint genes, encodes a protein kinase that is post-translationally modified after DNA damage. Like its yeast homologs, the Chk2/hCds1 protein phosphorylates Cdc25C in vitro, suggesting that it ar...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:

    authors: Chehab NH,Malikzay A,Appel M,Halazonetis TD

    更新日期:2000-02-01 00:00:00

  • Maternal Eed knockout causes loss of H3K27me3 imprinting and random X inactivation in the extraembryonic cells.

    abstract::Genomic imprinting is essential for mammalian development. Recent studies have revealed that maternal histone H3 Lys27 trimethylation (H3K27me3) can mediate DNA methylation-independent genomic imprinting. However, the regulatory mechanisms and functions of this new imprinting mechanism are largely unknown. Here we dem...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.318675.118

    authors: Inoue A,Chen Z,Yin Q,Zhang Y

    更新日期:2018-12-01 00:00:00

  • A nucleoprotein complex mediates the integration of retroviral DNA.

    abstract::The integration of viral DNA into the host genome is an essential step in the retrovirus life cycle. To understand this process better, we have examined the native state of viral DNA in cells acutely infected by murine leukemia virus (MLV), using both a physical assay for viral DNA and a functional assay for integrati...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.3.4.469

    authors: Bowerman B,Brown PO,Bishop JM,Varmus HE

    更新日期:1989-04-01 00:00:00

  • Chromatin and nucleosome dynamics in DNA damage and repair.

    abstract::Chromatin is organized into higher-order structures that form subcompartments in interphase nuclei. Different categories of specialized enzymes act on chromatin and regulate its compaction and biophysical characteristics in response to physiological conditions. We present an overview of the function of chromatin struc...

    journal_title:Genes & development

    pub_type: 杂志文章,评审

    doi:10.1101/gad.307702.117

    authors: Hauer MH,Gasser SM

    更新日期:2017-11-15 00:00:00

  • Sarkosyl defines three intermediate steps in transcription initiation by RNA polymerase III: application to stimulation of transcription by E1A.

    abstract::We used Sarkosyl to analyze steps along the pathway of transcription initiation by RNA polymerase III. Sarkosyl (0.015%) inhibited transcription when present prior to incubation of RNA polymerase III, TFIIIB, and TFIIIC with the VAI gene, whereas it had no detectable effect on initiation or reinitiation of transcripti...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.4.4.646

    authors: Kovelman R,Roeder RG

    更新日期:1990-04-01 00:00:00

  • The characterization of the TFIIIA synthesized in somatic cells of Xenopus laevis.

    abstract::In somatic cells of Xenopus, transcription of the TFIIIA gene initiates greater than 200 bp upstream from the start site used in oocytes. The resultant mRNA encodes a protein, S-TFIIIA, that is 22 amino acids longer at its amino terminus than the abundant form of TFIIIA in oocytes (O-TFIIIA). S-TFIIIA binds the 5S RNA...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.4.9.1602

    authors: Kim SH,Darby MK,Joho KE,Brown DD

    更新日期:1990-09-01 00:00:00

  • Inflammation and Hras signaling control epithelial-mesenchymal transition during skin tumor progression.

    abstract::Epithelial-mesenchymal transition (EMT) is thought to be an important, possibly essential, component of the process of tumor dissemination and metastasis. About 20%-30% of Hras mutant mouse skin carcinomas induced by chemical initiation/promotion protocols have undergone EMT. Reduced exposure to TPA-induced chronic in...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.210427.112

    authors: Wong CE,Yu JS,Quigley DA,To MD,Jen KY,Huang PY,Del Rosario R,Balmain A

    更新日期:2013-03-15 00:00:00

  • Control of cell division by a retinoblastoma protein homolog in Chlamydomonas.

    abstract::A key pathway that controls both cell division and differentiation in animal cells is mediated by the retinoblastoma (RB) family of tumor suppressors, which gate the passage of cells from G(1) to S and through S phase. The role(s) of the RB pathway in plants are not yet clearly defined, nor has there been any evidence...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.892101

    authors: Umen JG,Goodenough UW

    更新日期:2001-07-01 00:00:00

  • Haploinsufficient lethality and formation of arteriovenous malformations in Notch pathway mutants.

    abstract::The Notch signaling pathway is essential for embryonic vascular development in vertebrates. Here we show that mouse embryos heterozygous for a targeted mutation in the gene encoding the DLL4 ligand exhibit haploinsufficient lethality because of defects in vascular remodeling. We also describe vascular defects in embry...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1239204

    authors: Krebs LT,Shutter JR,Tanigaki K,Honjo T,Stark KL,Gridley T

    更新日期:2004-10-15 00:00:00

  • Critical residues for histone acetylation by Gcn5, functioning in Ada and SAGA complexes, are also required for transcriptional function in vivo.

    abstract::Several previously known transcription cofactors have been demonstrated in vitro recently to be histone acetyltransferases and deacetyltransferases, suggesting that remodeling of chromatin through histone acetylation plays a fundamental role in gene regulation. Clear evidence has not yet been obtained, however, to dem...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.12.5.640

    authors: Wang L,Liu L,Berger SL

    更新日期:1998-03-01 00:00:00

  • Induction of cell fate in the Drosophila retina: the bride of sevenless protein is predicted to contain a large extracellular domain and seven transmembrane segments.

    abstract::Previous genetic mosaic studies established that expression of the Drosophila bride of sevenless (boss) gene is required in photoreceptor neuron R8 for the development of photoreceptor neuron R7. This led to the proposal that boss encodes or regulates an R7-specific inductive cue. We have identified the boss gene base...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.4.11.1835

    authors: Hart AC,Krämer H,Van Vactor DL Jr,Paidhungat M,Zipursky SL

    更新日期:1990-11-01 00:00:00

  • The role of EKLF in human beta-globin gene competition.

    abstract::We have investigated the role of erythroid Kruppel-like factor (EKLF) in expression of the human beta-globin genes in compound EKLF knockout/human beta-locus transgenic mice. EKLF affects only the adult mouse beta-globin genes in homozygous knockout mice; heterozygous mice are unaffected. Here we show that EKLF knocko...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.10.22.2894

    authors: Wijgerde M,Gribnau J,Trimborn T,Nuez B,Philipsen S,Grosveld F,Fraser P

    更新日期:1996-11-15 00:00:00

  • Genome integrity and disease prevention in the nervous system.

    abstract::Multiple DNA repair pathways maintain genome stability and ensure that DNA remains essentially unchanged over the life of a cell. Various human diseases occur if DNA repair is compromised, and most of these impact the nervous system, in some cases exclusively. However, it is often unclear what specific endogenous dama...

    journal_title:Genes & development

    pub_type: 杂志文章,评审

    doi:10.1101/gad.301325.117

    authors: McKinnon PJ

    更新日期:2017-06-15 00:00:00

  • Embryonic lethality in mice homozygous for a targeted disruption of the N-myc gene.

    abstract::The N-myc gene encodes a putative transcription factor that is thought to function in the regulation of gene expression during cell differentiation and/or growth. To examine the role of N-myc during development, we have used targeted mutagenesis in embryonic stem cells to produce a mouse line that carries an N-myc nul...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.6.12a.2248

    authors: Charron J,Malynn BA,Fisher P,Stewart V,Jeannotte L,Goff SP,Robertson EJ,Alt FW

    更新日期:1992-12-01 00:00:00

  • CHD4/Mi-2beta activity is required for the positioning of the mesoderm/neuroectoderm boundary in Xenopus.

    abstract::Experiments in Xenopus have illustrated the importance of extracellular morphogens for embryonic gene regulation in vertebrates. Much less is known about how induction leads to the correct positioning of boundaries; for example, between germ layers. Here we report that the neuroectoderm/mesoderm boundary is controlled...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.409507

    authors: Linder B,Mentele E,Mansperger K,Straub T,Kremmer E,Rupp RA

    更新日期:2007-04-15 00:00:00

  • Hypersensitivity to DNA damage leads to increased apoptosis during early mouse development.

    abstract::Gastrulation in mice is associated with the start of extreme proliferation and differentiation. The potential cost to the embryo of a very rapid proliferation rate is a high production of damaged cells. We demonstrate a novel surveillance mechanism for the elimination of cells damaged by ionizing radiation during mous...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:

    authors: Heyer BS,MacAuley A,Behrendtsen O,Werb Z

    更新日期:2000-08-15 00:00:00