Regulation of the Drosophila apoptosome through feedback inhibition.

Abstract:

:Apoptosis is induced by caspases, which are members of the cysteine protease family. Caspases are synthesized as inactive zymogens and initiator caspases first gain activity by associating with an oligomeric complex of their adaptor proteins, such as the apoptosome. Activated initiator caspases subsequently cleave and activate effector caspases. Although such a proteolytic cascade would predict that a small number of active caspases could irreversibly amplify caspase activity and trigger apoptosis, many cells can maintain moderate levels of caspase activity to perform non-apoptotic roles in cellular differentiation, shape change and migration. Here we show that the Drosophila melanogaster apoptosome engages in a feedback inhibitory loop, which moderates its activation level in vivo. Specifically, the adaptor protein Apaf-1 lowers the level of its associated initiator caspase Dronc, without triggering apoptosis. Conversely, Dronc lowers Apaf-1 protein levels. This mutual suppression depends on the catalytic site of Dronc and a caspase cleavage site within Apaf-1. Moreover, the Drosophila inhibitor of apoptosis protein 1 (Diap1) is required for this process. We speculate that this feedback inhibition allows cells to regulate the degree of caspase activation for apoptotic and non-apoptotic purposes.

journal_name

Nat Cell Biol

journal_title

Nature cell biology

authors

Shapiro PJ,Hsu HH,Jung H,Robbins ES,Ryoo HD

doi

10.1038/ncb1803

subject

Has Abstract

pub_date

2008-12-01 00:00:00

pages

1440-6

issue

12

eissn

1465-7392

issn

1476-4679

pii

ncb1803

journal_volume

10

pub_type

杂志文章
  • Decrease in plasma membrane tension triggers PtdIns(4,5)P2 phase separation to inactivate TORC2.

    abstract::The target of rapamycin complex 2 (TORC2) plays a key role in maintaining the homeostasis of plasma membrane (PM) tension. TORC2 activation following increased PM tension involves redistribution of the Slm1 and 2 paralogues from PM invaginations known as eisosomes into membrane compartments containing TORC2. How Slm1/...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/s41556-018-0150-z

    authors: Riggi M,Niewola-Staszkowska K,Chiaruttini N,Colom A,Kusmider B,Mercier V,Soleimanpour S,Stahl M,Matile S,Roux A,Loewith R

    更新日期:2018-09-01 00:00:00

  • PDK1 regulates cancer cell motility by antagonising inhibition of ROCK1 by RhoE.

    abstract::In three-dimensional matrices cancer cells move with a rounded, amoeboid morphology that is controlled by ROCK-dependent contraction of acto-myosin. In this study, we show that PDK1 is required for phosphorylation of myosin light chain and cell motility, both on deformable gels and in vivo. Depletion of PDK1 alters th...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb1675

    authors: Pinner S,Sahai E

    更新日期:2008-02-01 00:00:00

  • LATS1 tumour suppressor affects cytokinesis by inhibiting LIMK1.

    abstract::LATS (large tumour suppressor) is a family of conserved tumour suppressors identified in Drosophila and mammals. Here we show that human LATS1 binds to LIMK1 in vitro and in vivo and colocalizes with LIMK1 at the actomyosin contractile ring during cytokinesis. LATS1 inhibits both the phosphorylation of cofilin by LIMK...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb1140

    authors: Yang X,Yu K,Hao Y,Li DM,Stewart R,Insogna KL,Xu T

    更新日期:2004-07-01 00:00:00

  • Apicobasal domain identities of expanding tubular membranes depend on glycosphingolipid biosynthesis.

    abstract::Metazoan internal organs are assembled from polarized tubular epithelia that must set aside an apical membrane domain as a lumenal surface. In a global Caenorhabditis elegans tubulogenesis screen, interference with several distinct fatty-acid-biosynthetic enzymes transformed a contiguous central intestinal lumen into ...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb2328

    authors: Zhang H,Abraham N,Khan LA,Hall DH,Fleming JT,Göbel V

    更新日期:2011-09-18 00:00:00

  • Reduced cytosolic protein synthesis suppresses mitochondrial degeneration.

    abstract::Mitochondrial function degenerates with ageing and in ageing-related neuromuscular degenerative diseases, causing physiological decline of the cell. Factors that can delay the degenerative process are actively sought after. Here, we show that reduced cytosolic protein synthesis is a robust cellular strategy that suppr...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb1769

    authors: Wang X,Zuo X,Kucejova B,Chen XJ

    更新日期:2008-09-01 00:00:00

  • Centrosomal MPF triggers the mitotic and morphogenetic switches of fission yeast.

    abstract::Activation of mitosis-promoting factor (MPF) drives mitotic commitment. In human cells active MPF appears first on centrosomes. We show that local activation of MPF on the equivalent organelle of fission yeast, the spindle pole body (SPB), promotes Polo kinase activity at the SPBs long before global MPF activation dri...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb2633

    authors: Grallert A,Patel A,Tallada VA,Chan KY,Bagley S,Krapp A,Simanis V,Hagan IM

    更新日期:2013-01-01 00:00:00

  • Prions remodel gene expression in yeast.

    abstract::Epigenetic mechanisms participate in the regulation of gene transcription in eukaryotes. Two studies in yeast have revealed an additional mechanism for controlling global gene transcription that is based on an inherited self-perpetuating change in the conformation of two different components of key transcriptional reg...

    journal_title:Nature cell biology

    pub_type: 评论,杂志文章

    doi:10.1038/ncb0309-241

    authors: Tuite MF,Cox BS

    更新日期:2009-03-01 00:00:00

  • Endoplasmic reticulum chaperone gp96 is required for innate immunity but not cell viability.

    abstract::Chaperone proteins are thought to promote the correct folding and assembly of newly synthesized proteins and to facilitate restoration of the folded state under environmental conditions that favour protein denaturation. They are among the most ubiquitous and highly conserved of all proteins. The eukaryotic endoplasmic...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb1001-891

    authors: Randow F,Seed B

    更新日期:2001-10-01 00:00:00

  • Single particle trajectories reveal active endoplasmic reticulum luminal flow.

    abstract::The endoplasmic reticulum (ER), a network of membranous sheets and pipes, supports functions encompassing biogenesis of secretory proteins and delivery of functional solutes throughout the cell1,2. Molecular mobility through the ER network enables these functionalities, but diffusion alone is not sufficient to explain...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/s41556-018-0192-2

    authors: Holcman D,Parutto P,Chambers JE,Fantham M,Young LJ,Marciniak SJ,Kaminski CF,Ron D,Avezov E

    更新日期:2018-10-01 00:00:00

  • Author Correction: Transient Scute activation via a self-stimulatory loop directs enteroendocrine cell pair specification from self-renewing intestinal stem cells.

    abstract::In the version of this Article originally published, the author had misnumbered the reference citations in the Methods, using numbers 1-14 instead of 46-59. These errors have now been corrected in all online versions of the Article. ...

    journal_title:Nature cell biology

    pub_type: 杂志文章,已发布勘误

    doi:10.1038/s41556-018-0053-z

    authors: Chen J,Xu N,Wang C,Huang P,Huang H,Jin Z,Yu Z,Cai T,Jiao R,Xi R

    更新日期:2018-08-01 00:00:00

  • The neural progenitor-specifying activity of FoxG1 is antagonistically regulated by CKI and FGF.

    abstract::FoxG1 is an evolutionarily conserved, winged-helix transcriptional repressor that maintains progenitor cells in the vertebrate forebrain. How the activity of FoxG1 is regulated is not known. Here, we report that in the developing Xenopus and mouse forebrain, FoxG1 is nuclear in progenitor cells but cytoplasmic in diff...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb1573

    authors: Regad T,Roth M,Bredenkamp N,Illing N,Papalopulu N

    更新日期:2007-05-01 00:00:00

  • Exocytosis of single chromaffin granules in cell-free inside-out membrane patches.

    abstract::In chromaffin cells, exocytosis of single granules and properties of the fusion pore--the first connection between vesicular lumen and extracellular space --can be studied by cell-attached patch amperometry, which couples patch-clamp capacitance measurements with simultaneous amperometric recordings of transmitter rel...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb956

    authors: Dernick G,Alvarez de Toledo G,Lindau M

    更新日期:2003-04-01 00:00:00

  • Dynamics and retention of misfolded proteins in native ER membranes.

    abstract::When co-translationally inserted into endoplasmic reticulum (ER) membranes, newly synthesized proteins encounter the lumenal environment of the ER, which contains chaperone proteins that facilitate the folding reactions necessary for protein oligomerization, maturation and export from the ER. Here we show, using a tem...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/35010558

    authors: Nehls S,Snapp EL,Cole NB,Zaal KJ,Kenworthy AK,Roberts TH,Ellenberg J,Presley JF,Siggia E,Lippincott-Schwartz J

    更新日期:2000-05-01 00:00:00

  • New neuropeptides containing carboxy-terminal RFamide and their receptor in mammals.

    abstract::Only a few RFamide peptides have been identified in mammals, although they have been abundantly found in invertebrates. Here we report the identification of a human gene that encodes at least three RFamide-related peptides, hRFRP-1-3. Cells transfected with a seven-transmembrane-domain receptor, OT7T022, specifically ...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/35036326

    authors: Hinuma S,Shintani Y,Fukusumi S,Iijima N,Matsumoto Y,Hosoya M,Fujii R,Watanabe T,Kikuchi K,Terao Y,Yano T,Yamamoto T,Kawamata Y,Habata Y,Asada M,Kitada C,Kurokawa T,Onda H,Nishimura O,Tanaka M,Ibata Y,Fujino M

    更新日期:2000-10-01 00:00:00

  • Dynein branches out.

    abstract::Individual neurons form specific elaborate dendritic structures that receive presynaptic information. The pattern of dendritic branching is regulated by the microtubule-associated motor protein dynein, which is responsible for the transport of essential endosomes and other organelles into the dendrites. ...

    journal_title:Nature cell biology

    pub_type: 评论,杂志文章

    doi:10.1038/ncb1008-1131

    authors: Tear G

    更新日期:2008-10-01 00:00:00

  • Tissue-specific CTCF-cohesin-mediated chromatin architecture delimits enhancer interactions and function in vivo.

    abstract::The genome is organized via CTCF-cohesin-binding sites, which partition chromosomes into 1-5 megabase (Mb) topologically associated domains (TADs), and further into smaller sub-domains (sub-TADs). Here we examined in vivo an ∼80 kb sub-TAD, containing the mouse α-globin gene cluster, lying within a ∼1 Mb TAD. We find ...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb3573

    authors: Hanssen LLP,Kassouf MT,Oudelaar AM,Biggs D,Preece C,Downes DJ,Gosden M,Sharpe JA,Sloane-Stanley JA,Hughes JR,Davies B,Higgs DR

    更新日期:2017-08-01 00:00:00

  • Cellular energy stress induces AMPK-mediated regulation of YAP and the Hippo pathway.

    abstract::YAP (Yes-associated protein) is a transcription co-activator in the Hippo tumour suppressor pathway and controls cell growth, tissue homeostasis and organ size. YAP is inhibited by the kinase Lats, which phosphorylates YAP to induce its cytoplasmic localization and proteasomal degradation. YAP induces gene expression ...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb3111

    authors: Mo JS,Meng Z,Kim YC,Park HW,Hansen CG,Kim S,Lim DS,Guan KL

    更新日期:2015-04-01 00:00:00

  • Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation.

    abstract::The heterogeneity of exosomal populations has hindered our understanding of their biogenesis, molecular composition, biodistribution and functions. By employing asymmetric flow field-flow fractionation (AF4), we identified two exosome subpopulations (large exosome vesicles, Exo-L, 90-120 nm; small exosome vesicles, Ex...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/s41556-018-0040-4

    authors: Zhang H,Freitas D,Kim HS,Fabijanic K,Li Z,Chen H,Mark MT,Molina H,Martin AB,Bojmar L,Fang J,Rampersaud S,Hoshino A,Matei I,Kenific CM,Nakajima M,Mutvei AP,Sansone P,Buehring W,Wang H,Jimenez JP,Cohen-Gould L,P

    更新日期:2018-03-01 00:00:00

  • Caenorhabditis elegans transthyretin-like protein TTR-52 mediates recognition of apoptotic cells by the CED-1 phagocyte receptor.

    abstract::During apoptosis, dying cells are swiftly removed by phagocytes. It is not fully understood how apoptotic cells are recognized by phagocytes. Here we report the identification and characterization of the Caenorhabditis elegans ttr-52 gene, which encodes a transthyretin-like protein and is required for efficient cell c...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb2068

    authors: Wang X,Li W,Zhao D,Liu B,Shi Y,Chen B,Yang H,Guo P,Geng X,Shang Z,Peden E,Kage-Nakadai E,Mitani S,Xue D

    更新日期:2010-07-01 00:00:00

  • Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts.

    abstract::To learn more about cancer-associated fibroblasts (CAFs), we have isolated fibroblasts from different stages of breast cancer progression and analysed their function and gene expression. These analyses reveal that activation of the YAP transcription factor is a signature feature of CAFs. YAP function is required for C...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb2756

    authors: Calvo F,Ege N,Grande-Garcia A,Hooper S,Jenkins RP,Chaudhry SI,Harrington K,Williamson P,Moeendarbary E,Charras G,Sahai E

    更新日期:2013-06-01 00:00:00

  • DNA processing is not required for ATM-mediated telomere damage response after TRF2 deletion.

    abstract::Telomere attrition and other forms of telomere damage can activate the ATM kinase pathway. What generates the DNA damage signal at mammalian chromosome ends or at other double-strand breaks is not known. Telomere dysfunction is often accompanied by disappearance of the 3' telomeric overhang, raising the possibility th...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb1275

    authors: Celli GB,de Lange T

    更新日期:2005-07-01 00:00:00

  • F-actin dismantling through a redox-driven synergy between Mical and cofilin.

    abstract::Numerous cellular functions depend on actin filament (F-actin) disassembly. The best-characterized disassembly proteins, the ADF (actin-depolymerizing factor)/cofilins (encoded by the twinstar gene in Drosophila), sever filaments and recycle monomers to promote actin assembly. Cofilin is also a relatively weak actin d...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb3390

    authors: Grintsevich EE,Yesilyurt HG,Rich SK,Hung RJ,Terman JR,Reisler E

    更新日期:2016-08-01 00:00:00

  • Protein kinase activity of phosphoinositide 3-kinase regulates beta-adrenergic receptor endocytosis.

    abstract::Phosphoinositide 3-kinase (PI(3)K) is a unique enzyme characterized by both lipid and protein kinase activities. Here, we demonstrate a requirement for the protein kinase activity of PI(3)K in agonist-dependent beta-adrenergic receptor (betaAR) internalization. Using PI(3)K mutants with either protein or lipid phospho...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb1278

    authors: Naga Prasad SV,Jayatilleke A,Madamanchi A,Rockman HA

    更新日期:2005-08-01 00:00:00

  • Maintaining integrity.

    abstract::Research on genome stability and integrity now extends far beyond the biochemistry of DNA repair to encompass signal transduction pathways that span numerous aspects of cellular life. Derailed genomic integrity pathways can result in debilitating genetic disorders, premature ageing, predisposition to cancer and degene...

    journal_title:Nature cell biology

    pub_type:

    doi:10.1038/ncb1004-923

    authors: Shiloh Y,Lehmann AR

    更新日期:2004-10-01 00:00:00

  • Pten regulates spindle pole movement through Dlg1-mediated recruitment of Eg5 to centrosomes.

    abstract::Phosphatase and tensin homologue (Pten) suppresses neoplastic growth by negatively regulating PI(3)K signalling through its phosphatase activity. To gain insight into the actions of non-catalytic Pten domains in normal physiological processes and tumorigenesis, we engineered mice lacking the PDZ-binding domain (PDZ-BD...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb3369

    authors: van Ree JH,Nam HJ,Jeganathan KB,Kanakkanthara A,van Deursen JM

    更新日期:2016-07-01 00:00:00

  • CDK1-dependent phosphorylation of EZH2 suppresses methylation of H3K27 and promotes osteogenic differentiation of human mesenchymal stem cells.

    abstract::Enhancer of zeste homologue 2 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 (PRC2) and catalyses the trimethylation of histone H3 on Lys 27 (H3K27), which represses gene transcription. EZH2 enhances cancer-cell invasiveness and regulates stem cell differentiation. Here, we demonstrate that EZH2 can ...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb2139

    authors: Wei Y,Chen YH,Li LY,Lang J,Yeh SP,Shi B,Yang CC,Yang JY,Lin CY,Lai CC,Hung MC

    更新日期:2011-01-01 00:00:00

  • Rubicon swaps autophagy for LAP.

    abstract::Phagocytic cells engulf their prey into vesicular structures called phagosomes, of which a certain proportion becomes demarcated for enhanced maturation by a process called LC3-associated phagocytosis (LAP). Light has now been shed on the molecular requirements of LAP, establishing a central role for the protein Rubic...

    journal_title:Nature cell biology

    pub_type: 评论,杂志文章

    doi:10.1038/ncb3197

    authors: Boyle KB,Randow F

    更新日期:2015-07-01 00:00:00

  • Author Correction: Mapping the proximity interaction network of the Rho-family GTPases reveals signalling pathways and regulatory mechanisms.

    abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title:Nature cell biology

    pub_type: 杂志文章,已发布勘误

    doi:10.1038/s41556-020-0479-y

    authors: Bagci H,Sriskandarajah N,Robert A,Boulais J,Elkholi IE,Tran V,Lin ZY,Thibault MP,Dubé N,Faubert D,Hipfner DR,Gingras AC,Côté JF

    更新日期:2020-03-01 00:00:00

  • Activator-inhibitor coupling between Rho signalling and actin assembly makes the cell cortex an excitable medium.

    abstract::Animal cell cytokinesis results from patterned activation of the small GTPase Rho, which directs assembly of actomyosin in the equatorial cortex. Cytokinesis is restricted to a portion of the cell cycle following anaphase onset in which the cortex is responsive to signals from the spindle. We show that shortly after a...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb3251

    authors: Bement WM,Leda M,Moe AM,Kita AM,Larson ME,Golding AE,Pfeuti C,Su KC,Miller AL,Goryachev AB,von Dassow G

    更新日期:2015-11-01 00:00:00

  • Cytoplasmic ubiquitin ligase KPC regulates proteolysis of p27(Kip1) at G1 phase.

    abstract::The cyclin-dependent kinase inhibitor p27(Kip1) is degraded at the G0-G1 transition of the cell cycle by the ubiquitin-proteasome pathway. Although the nuclear ubiquitin ligase (E3) SCF(Skp2) is implicated in p27(Kip1) degradation, proteolysis of p27(Kip1) at the G0-G1 transition proceeds normally in Skp2(-/-) cells. ...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb1194

    authors: Kamura T,Hara T,Matsumoto M,Ishida N,Okumura F,Hatakeyama S,Yoshida M,Nakayama K,Nakayama KI

    更新日期:2004-12-01 00:00:00