Caspase activity is required for engulfment of apoptotic cells.

Abstract:

:Clearance of apoptotic cells by phagocytic neighbors is crucial for normal development of multicellular organisms. However, how phagocytes discriminate between healthy and dying cells remains poorly understood. We focus on glial phagocytosis of apoptotic neurons during development of the Drosophila central nervous system. We identified phosphatidylserine (PS) as a ligand on apoptotic cells for the phagocytic receptor Six Microns Under (SIMU) and report that PS alone is not sufficient for engulfment. Our data reveal that, additionally to PS exposure, caspase activity is required for clearance of apoptotic cells by phagocytes. Here we demonstrate that SIMU recognizes and binds PS on apoptotic cells through its N-terminal EMILIN (EMI), Nimrod 1 (NIM1), and NIM2 repeats, whereas the C-terminal NIM3 and NIM4 repeats control SIMU affinity to PS. Based on the structure-function analysis of SIMU, we discovered a novel mechanism of internal inhibition responsible for differential affinities of SIMU to its ligand which might prevent elimination of living cells exposing PS on their surfaces.

journal_name

Mol Cell Biol

authors

Shklyar B,Levy-Adam F,Mishnaevski K,Kurant E

doi

10.1128/MCB.00233-13

subject

Has Abstract

pub_date

2013-08-01 00:00:00

pages

3191-201

issue

16

eissn

0270-7306

issn

1098-5549

pii

MCB.00233-13

journal_volume

33

pub_type

杂志文章
  • Peroxisome proliferator-activated receptor alpha regulates a microRNA-mediated signaling cascade responsible for hepatocellular proliferation.

    abstract::Activation of peroxisome proliferator-activated receptor alpha (PPARalpha) leads to hepatocellular proliferation and liver carcinomas. The early events mediating these effects are unknown. A novel mechanism by which PPARalpha regulates gene expression and hepatocellular proliferation was uncovered. MicroRNA (miRNA) ex...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00317-07

    authors: Shah YM,Morimura K,Yang Q,Tanabe T,Takagi M,Gonzalez FJ

    更新日期:2007-06-01 00:00:00

  • Cdx protein interaction with Hoxa5 regulatory sequences contributes to Hoxa5 regional expression along the axial skeleton.

    abstract::Hox gene functions are intimately linked to correct developmental expression of the genes. The identification of cis-acting regulatory sequences and their associated trans-acting factors constitutes a key step in deciphering the mechanisms underlying the correct positioning of the functional domain of Hox genes along ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.25.4.1389-1401.2005

    authors: Tabariès S,Lapointe J,Besch T,Carter M,Woollard J,Tuggle CK,Jeannotte L

    更新日期:2005-02-01 00:00:00

  • Isolation and characterization of cloned DNA sequences containing ribosomal protein genes of Drosophila melanogaster.

    abstract::Ribosomal (r) proteins encoded by polyadenylated RNA were specifically precipitated in vitro from polysomes by using antibodies raised against characterized Drosophila melanogaster r proteins. The immuno-purified mRNA in the polysome complex was used to prepare cDNA with which to probe a D. melanogaster genomic librar...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.4.12.2643

    authors: Burns DK,Stark BC,Macklin MD,Chooi WY

    更新日期:1984-12-01 00:00:00

  • IkappaB kinase beta phosphorylates the K63 deubiquitinase A20 to cause feedback inhibition of the NF-kappaB pathway.

    abstract::Misregulation of NF-kappaB signaling leads to infectious, inflammatory, or autoimmune disorders. IkappaB kinase beta (IKKbeta) is an essential activator of NF-kappaB and is known to phosphorylate the NF-kappaB inhibitor, IkappaBalpha, allowing it to undergo ubiquitin-mediated proteasomal degradation. However, beyond I...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01101-07

    authors: Hutti JE,Turk BE,Asara JM,Ma A,Cantley LC,Abbott DW

    更新日期:2007-11-01 00:00:00

  • Enhancer blocking activity of the insulator at H19-ICR is independent of chromatin barrier establishment.

    abstract::Transcriptional insulators are cis regulatory elements that organize chromatin into independently regulated domains. At the imprinted murine Igf2/H19 locus, the H19-ICR insulator prevents the activation of the Igf2 promoter on the maternal allele by enhancers that activate H19 on the same chromosome. Given the well-de...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00091-08

    authors: Singh V,Srivastava M

    更新日期:2008-06-01 00:00:00

  • RIP1 Cleavage in the Kinase Domain Regulates TRAIL-Induced NF-κB Activation and Lymphoma Survival.

    abstract::Although TRAIL is considered a potential anticancer agent, it enhances tumor progression by activating NF-κB in apoptosis-resistant cells. Cellular FLICE-like inhibitory protein (cFLIP) overexpression and caspase-8 activation have been implicated in TRAIL-induced NF-κB activation; however, the underlying mechanisms ar...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00692-15

    authors: Zhang L,Blackwell K,Workman LM,Chen S,Pope MR,Janz S,Habelhah H

    更新日期:2015-10-01 00:00:00

  • Site-directed perturbation of protein kinase C- integrin interaction blocks carcinoma cell chemotaxis.

    abstract::Polarized cell movement is an essential requisite for cancer metastasis; thus, interference with the tumor cell motility machinery would significantly modify its metastatic behavior. Protein kinase C alpha (PKC alpha) has been implicated in the promotion of a migratory cell phenotype. We report that the phorbol ester-...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.22.16.5897-5911.2002

    authors: Parsons M,Keppler MD,Kline A,Messent A,Humphries MJ,Gilchrist R,Hart IR,Quittau-Prevostel C,Hughes WE,Parker PJ,Ng T

    更新日期:2002-08-01 00:00:00

  • Identification of distal cis-regulatory elements at mouse mitoferrin loci using zebrafish transgenesis.

    abstract::Mitoferrin 1 (Mfrn1; Slc25a37) and mitoferrin 2 (Mfrn2; Slc25a28) function as essential mitochondrial iron importers for heme and Fe/S cluster biogenesis. A genetic deficiency of Mfrn1 results in a profound hypochromic anemia in vertebrate species. To map the cis-regulatory modules (CRMs) that control expression of th...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01010-10

    authors: Amigo JD,Yu M,Troadec MB,Gwynn B,Cooney JD,Lambert AJ,Chi NC,Weiss MJ,Peters LL,Kaplan J,Cantor AB,Paw BH

    更新日期:2011-04-01 00:00:00

  • Regulation of histone mRNA production and stability in serum-stimulated mouse 3T6 fibroblasts.

    abstract::We measured the content and metabolism of histone mRNA in mouse 3T6 fibroblasts during a serum-induced transition from the resting to growing state. The content of several histone H3 and H2b mRNAs was measured by an S1 nuclease procedure. All of these increase in parallel by a factor of about 50 during S phase. Howeve...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.3.11.1920

    authors: DeLisle AJ,Graves RA,Marzluff WF,Johnson LF

    更新日期:1983-11-01 00:00:00

  • Dynamic localization and function of Bni1p at the sites of directed growth in Saccharomyces cerevisiae.

    abstract::Formin homology (FH) proteins are implicated in cell polarization and cytokinesis through actin organization. There are two FH proteins in the yeast Saccharomyces cerevisiae, Bni1p and Bnr1p. Bni1p physically interacts with Rho family small G proteins (Rho1p and Cdc42p), actin, two actin-binding proteins (profilin and...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.3.827-839.2001

    authors: Ozaki-Kuroda K,Yamamoto Y,Nohara H,Kinoshita M,Fujiwara T,Irie K,Takai Y

    更新日期:2001-02-01 00:00:00

  • Can ACG serve as an initiation codon for protein synthesis in eucaryotic cells?

    abstract::An ACG codon, which replaces the AUG codon used to initiate the synthesis of bacteriophage T7 gene 0.3 protein, was shown to function as a low-efficiency initiation codon in a wheat germ cell-free protein-synthesizing system. ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.5.12.3621

    authors: Anderson CW,Buzash-Pollert E

    更新日期:1985-12-01 00:00:00

  • Nuclease-deficient FEN-1 blocks Rad51/BRCA1-mediated repair and causes trinucleotide repeat instability.

    abstract::Previous studies have shown that expansion-prone repeats form structures that inhibit human flap endonuclease (FEN-1). We report here that faulty processing by FEN-1 initiates repeat instability in mammalian cells. Disease-length CAG tracts in Huntington's disease mice heterozygous for FEN-1 display a tendency toward ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.17.6063-6074.2003

    authors: Spiro C,McMurray CT

    更新日期:2003-09-01 00:00:00

  • Renal Anemia Model Mouse Established by Transgenic Rescue with an Erythropoietin Gene Lacking Kidney-Specific Regulatory Elements.

    abstract::The erythropoietin (Epo) gene is under tissue-specific inducible regulation. Because the kidney is the primary EPO-producing tissue in adults, impaired EPO production in chronic kidney disorders results in serious renal anemia. The Epo gene contains a liver-specific enhancer in the 3' region, but the kidney-specific e...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00451-16

    authors: Hirano I,Suzuki N,Yamazaki S,Sekine H,Minegishi N,Shimizu R,Yamamoto M

    更新日期:2017-02-01 00:00:00

  • RNA-mediated gene duplication: the rat preproinsulin I gene is a functional retroposon.

    abstract::Rats and mice have two, equally expressed, nonallelic genes encoding preproinsulin (genes I and II). Cytological hybridization with metaphase chromosomes indicated that both genes reside on rat chromosome I but are approximately 100,000 kilobases apart. In mice the two genes reside on two different chromosomes. DNA se...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.5.8.2090

    authors: Soares MB,Schon E,Henderson A,Karathanasis SK,Cate R,Zeitlin S,Chirgwin J,Efstratiadis A

    更新日期:1985-08-01 00:00:00

  • Imprinted Nesp55 influences behavioral reactivity to novel environments.

    abstract::Genomic imprinting results in parent-of-origin-dependent monoallelic expression of selected genes. Although their importance in development and physiology is recognized, few imprinted genes have been investigated for their effects on brain function. Gnas is a complex imprinted locus whose gene products are involved in...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.25.8.3019-3026.2005

    authors: Plagge A,Isles AR,Gordon E,Humby T,Dean W,Gritsch S,Fischer-Colbrie R,Wilkinson LS,Kelsey G

    更新日期:2005-04-01 00:00:00

  • Receptor isoforms mediate opposing proliferative effects through gbetagamma-activated p38 or Akt pathways.

    abstract::The opposing effects on proliferation mediated by G-protein-coupled receptor isoforms differing in their COOH termini could be correlated with the abilities of the receptors to differentially activate p38, implicated in apoptotic events, or phosphatidylinositol 3-kinase (PI 3-K), which provides a source of survival si...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.16.5974-5985.2000

    authors: Sellers LA,Alderton F,Carruthers AM,Schindler M,Humphrey PP

    更新日期:2000-08-01 00:00:00

  • Receptor clustering is involved in Reelin signaling.

    abstract::The Reelin signaling cascade plays a crucial role in the correct positioning of neurons during embryonic brain development. Reelin binding to apolipoprotein E receptor 2 (ApoER2) and very-low-density-lipoprotein receptor (VLDLR) leads to phosphorylation of disabled 1 (Dab1), an adaptor protein which associates with th...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.24.3.1378-1386.2004

    authors: Strasser V,Fasching D,Hauser C,Mayer H,Bock HH,Hiesberger T,Herz J,Weeber EJ,Sweatt JD,Pramatarova A,Howell B,Schneider WJ,Nimpf J

    更新日期:2004-02-01 00:00:00

  • Regulation of cyclin D-dependent kinase 4 (cdk4) by cdk4-activating kinase.

    abstract::The accumulation of assembled holoenzymes composed of regulatory D-type cyclins and their catalytic partner, cyclin-dependent kinase 4 (cdk4), is rate limiting for progression through the G1 phase of the cell cycle in mammalian fibroblasts. Both the synthesis and assembly of D-type cyclins and cdk4 depend upon serum s...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.14.4.2713

    authors: Kato JY,Matsuoka M,Strom DK,Sherr CJ

    更新日期:1994-04-01 00:00:00

  • Generation of mice deficient in both KLF3/BKLF and KLF8 reveals a genetic interaction and a role for these factors in embryonic globin gene silencing.

    abstract::Krüppel-like factors 3 and 8 (KLF3 and KLF8) are highly related transcriptional regulators that bind to similar sequences of DNA. We have previously shown that in erythroid cells there is a regulatory hierarchy within the KLF family, whereby KLF1 drives the expression of both the Klf3 and Klf8 genes and KLF3 in turn r...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00074-13

    authors: Funnell AP,Mak KS,Twine NA,Pelka GJ,Norton LJ,Radziewic T,Power M,Wilkins MR,Bell-Anderson KS,Fraser ST,Perkins AC,Tam PP,Pearson RC,Crossley M

    更新日期:2013-08-01 00:00:00

  • Two conserved amino acid motifs mediate protein targeting to the micronemes of the apicomplexan parasite Toxoplasma gondii.

    abstract::The micronemal protein 2 (MIC2) of Toxoplasma gondii shares sequence and structural similarities with a series of adhesive molecules of different apicomplexan parasites. These molecules accumulate, through a yet unknown mechanism, in secretory vesicles (micronemes), which together with tubular and membrane structures ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.19.7332-7341.2000

    authors: Di Cristina M,Spaccapelo R,Soldati D,Bistoni F,Crisanti A

    更新日期:2000-10-01 00:00:00

  • Nucleosome translational position, not histone acetylation, determines TFIIIA binding to nucleosomal Xenopus laevis 5S rRNA genes.

    abstract::We sought to study the binding constraints placed on the nine-zinc-finger protein transcription factor IIIA (TFIIIA) by a histone octamer. To this end, five overlapping fragments of the Xenopus laevis oocyte and somatic 5S rRNA genes were reconstituted into nucleosomes, and it was subsequently shown that nucleosome tr...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.18.3.1156

    authors: Howe L,Ausió J

    更新日期:1998-03-01 00:00:00

  • Activation and inhibition of erythropoietin receptor function: role of receptor dimerization.

    abstract::Members of the cytokine receptor superfamily have structurally similar extracellular ligand-binding domains yet diverse cytoplasmic regions lacking any obvious catalytic domains. Many of these receptors form ligand-induced oligomers which are likely to participate in transmembrane signaling. A constitutively active (f...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.14.6.3535

    authors: Watowich SS,Hilton DJ,Lodish HF

    更新日期:1994-06-01 00:00:00

  • Pdc1 functions in the assembly of P bodies in Schizosaccharomyces pombe.

    abstract::P bodies are cytoplasmic RNA granules containing the Dcp1-Dcp2 decapping enzymes where mRNA decay can occur. Here, we describe the characterization of P bodies in the fission yeast Schizosaccharomyces pombe. Most information on the property and function of P bodies stems from studies in the distantly related budding y...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01583-12

    authors: Wang CY,Chen WL,Wang SW

    更新日期:2013-03-01 00:00:00

  • RasGAP-associated endoribonuclease G3Bp: selective RNA degradation and phosphorylation-dependent localization.

    abstract::Mitogen activation of mRNA decay pathways likely involves specific endoribonucleases, such as G3BP, a phosphorylation-dependent endoribonuclease that associates with RasGAP in dividing but not quiescent cells. G3BP exclusively cleaves between cytosine and adenine (CA) after a specific interaction with RNA through the ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.22.7747-7760.2001

    authors: Tourrière H,Gallouzi IE,Chebli K,Capony JP,Mouaikel J,van der Geer P,Tazi J

    更新日期:2001-11-01 00:00:00

  • Pairing between gypsy insulators facilitates the enhancer action in trans throughout the Drosophila genome.

    abstract::The Suppressor of the Hairy wing [Su(Hw)] binding region within the gypsy retrotransposon is the best known chromatin insulator in Drosophila melanogaster. According to previous data, two copies of the gypsy insulator inserted between an enhancer and a promoter neutralize each other's actions, which is indicative of a...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.25.21.9283-9291.2005

    authors: Kravchenko E,Savitskaya E,Kravchuk O,Parshikov A,Georgiev P,Savitsky M

    更新日期:2005-11-01 00:00:00

  • Detection of two chromatin proteins which bind specifically to the 5'-flanking region of the rat prolactin gene.

    abstract::We employed a protein gel blotting procedure to search for nuclear proteins from rat pituitary cells that bind preferentially to the 5'-flanking region of the rat prolactin gene. By gel blots of chromatin proteins from GH3 rat pituitary tumor cells with a 32P-labeled prolactin genomic clone, we detected two major bind...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.5.11.2967

    authors: White BA,Preston GM,Lufkin TC,Bancroft C

    更新日期:1985-11-01 00:00:00

  • A human globin enhancer causes both discrete and widespread alterations in chromatin structure.

    abstract::Gene activation requires alteration of chromatin structure to facilitate active transcription complex formation at a gene promoter. Nucleosome remodeling complexes and histone modifying complexes each play unique and interdependent roles in bringing about these changes. The role of distant enhancers in these structura...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.22.8099-8109.2003

    authors: Kim A,Dean A

    更新日期:2003-11-01 00:00:00

  • A severely defective TATA-binding protein-TFIIB interaction does not preclude transcriptional activation in vivo.

    abstract::In yeast cells, mutations in the TATA-binding protein (TBP) that disrupt the interaction with the TATA element or with TFIIA can selectively impair the response to acidic activator proteins. We analyzed the transcriptional properties of TBP derivatives in which residues that directly interact with TFIIB were replaced ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.3.1336

    authors: Lee M,Struhl K

    更新日期:1997-03-01 00:00:00

  • The hypoxia-inducible factor 1/NOR-1 axis regulates the survival response of endothelial cells to hypoxia.

    abstract::Hypoxia induces apoptosis but also triggers adaptive mechanisms to ensure cell survival. Here we show that the prosurvival effects of hypoxia-inducible factor 1 (HIF-1) in endothelial cells are mediated by neuron-derived orphan receptor 1 (NOR-1). The overexpression of NOR-1 decreased the rate of endothelial cells und...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00945-09

    authors: Martorell L,Gentile M,Rius J,Rodríguez C,Crespo J,Badimon L,Martínez-González J

    更新日期:2009-11-01 00:00:00

  • Peroxisome proliferator-activated receptor gamma target gene encoding a novel angiopoietin-related protein associated with adipose differentiation.

    abstract::The nuclear receptor peroxisome proliferator-activated receptor gamma regulates adipose differentiation and systemic insulin signaling via ligand-dependent transcriptional activation of target genes. However, the identities of the biologically relevant target genes are largely unknown. Here we describe the isolation a...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.14.5343-5349.2000

    authors: Yoon JC,Chickering TW,Rosen ED,Dussault B,Qin Y,Soukas A,Friedman JM,Holmes WE,Spiegelman BM

    更新日期:2000-07-01 00:00:00