Abstract:
:Vaccinia virus, a close relative of the causative agent of smallpox, exploits actin polymerization to enhance its cell-to-cell spread. We show that actin-based motility of vaccinia is initiated only at the plasma membrane and remains associated with it. There must therefore be another form of cytoplasmic viral transport, from the cell centre, where the virus replicates, to the periphery. Video analysis reveals that GFP-labelled intracellular enveloped virus particles (IEVs) move from their perinuclear site of assembly to the plasma membrane on microtubules. We show that the viral membrane protein A36R, which is essential for actin-based motility of vaccinia, is also involved in microtubule-mediated movement of IEVs. We further show that conventional kinesin is recruited to IEVs via the light chain TPR repeats and is required for microtubule-based motility of the virus. Vaccinia thus sequentially exploits the microtubule and actin cytoskeletons to enhance its cell-to-cell spread.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Rietdorf J,Ploubidou A,Reckmann I,Holmström A,Frischknecht F,Zettl M,Zimmermann T,Way Mdoi
10.1038/ncb1101-992keywords:
subject
Has Abstractpub_date
2001-11-01 00:00:00pages
992-1000issue
11eissn
1465-7392issn
1476-4679pii
ncb1101-992journal_volume
3pub_type
杂志文章abstract::We have designed new non-peptidic potential inhibitors of gamma-secretase and examined their ability to prevent production of amyloid-beta 40 (Abeta40) and Abeta42 by human cells expressing wild-type and Swedish-mutant beta-amyloid precursor protein (betaAPP). Here we identify three such agents that markedly reduce re...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/35074581
更新日期:2001-05-01 00:00:00
abstract::Haematopoietic stem-progenitor cells (HSPCs) reside in the bone marrow niche, where interactions with osteoblasts provide essential cues for their proliferation and survival. Here, we use live-cell imaging to characterize both the site of contact between osteoblasts and haematopoietic progenitor cells (HPCs) and event...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb1838
更新日期:2009-03-01 00:00:00
abstract::Pyruvate kinase M2 (PKM2) is upregulated in multiple cancer types and contributes to the Warburg effect by unclear mechanisms. Here we demonstrate that EGFR-activated ERK2 binds directly to PKM2 Ile 429/Leu 431 through the ERK2 docking groove and phosphorylates PKM2 at Ser 37, but does not phosphorylate PKM1. Phosphor...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb2629
更新日期:2012-12-01 00:00:00
abstract::TP53 (tumour protein 53) is one of the most frequently mutated genes in human cancer and its role during cellular transformation has been studied extensively. However, the homeostatic functions of p53 are less well understood. Here, we explore the molecular dependency network of TP53 through an RNAi-mediated synthetic...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb2264
更新日期:2011-06-05 00:00:00
abstract::The adult organism is characterized by remarkable plasticity, which enables efficient regeneration and restoration of homeostasis after damage. When aberrantly activated, this plasticity contributes to tumour initiation and progression. Here we review recent advances in this field with a focus on cell fate changes and...
journal_title:Nature cell biology
pub_type: 杂志文章,评审
doi:10.1038/ncb3611
更新日期:2017-10-01 00:00:00
abstract::The Notch1 gene has an important role in mammalian cell-fate decision and tumorigenesis. Upstream control mechanisms for transcription of this gene are still poorly understood. In a chemical genetics screen for small molecule activators of Notch signalling, we identified epidermal growth factor receptor (EGFR) as a ke...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb1750
更新日期:2008-08-01 00:00:00
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
更新日期:2018-08-01 00:00:00
abstract::In Huntington disease, polyglutamine expansion of the protein huntingtin (Htt) leads to selective neurodegenerative loss of medium spiny neurons throughout the striatum by an unknown apoptotic mechanism. Binding of Hip-1, a protein normally associated with Htt, is reduced by polyglutamine expansion. Free Hip-1 binds t...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb735
更新日期:2002-02-01 00:00:00
abstract::Programmed cell death (apoptosis) is used by multicellular organisms during development and to maintain homeostasis within mature tissues. One of the first genes shown to regulate apoptosis was bcl-2. Subsequently, a number of Bcl-2-related proteins have been identified. Despite overwhelming evidence that Bcl-2 protei...
journal_title:Nature cell biology
pub_type: 杂志文章,评审
doi:10.1038/70237
更新日期:1999-12-01 00:00:00
abstract::The emergence of resistance to poly-ADP-ribose polymerase inhibitors (PARPi) poses a threat to the treatment of BRCA1 and BRCA2 (BRCA1/2)-deficient tumours. Stabilization of stalled DNA replication forks is a recently identified PARPi-resistance mechanism that promotes genomic stability in BRCA1/2-deficient cancers. D...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb3626
更新日期:2017-11-01 00:00:00
abstract::Proteins essential for vesicle formation by the Coat Protein I (COPI) complex are being identified, but less is known about the role of specific lipids. Brefeldin-A ADP-ribosylated substrate (BARS) functions in the fission step of COPI vesicle formation. Here, we show that BARS induces membrane curvature in cooperatio...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb1774
更新日期:2008-10-01 00:00:00
abstract::Cancer-induced immune responses affect tumour progression and therapeutic response. In multiple murine models and clinical datasets, we identified large variations of neutrophils and macrophages that define 'immune subtypes' of triple-negative breast cancer (TNBC), including neutrophil-enriched (NES) and macrophage-en...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/s41556-019-0373-7
更新日期:2019-09-01 00:00:00
abstract::The migration of border cells during Drosophila melanogaster oogenesis is a simple and powerful system for studying invasive cell migration in vivo. Border cells are somatic cells that delaminate from the follicular epithelium of an egg chamber and invade the germ line cluster. They migrate between the nurse cells to ...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb848
更新日期:2002-09-01 00:00:00
abstract::The polarity protein Scribble (SCRIB) regulates apical-basal polarity, directional migration and tumour suppression in Drosophila and mammals. Here we report that SCRIB is an important regulator of myeloid cell functions including bacterial infection and inflammation. SCRIB interacts directly with the NADPH oxidase (N...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb3413
更新日期:2016-11-01 00:00:00
abstract::The presence of disseminated tumour cells (DTCs) in bone marrow is predictive of poor metastasis-free survival of patients with breast cancer with localized disease. DTCs persist in distant tissues despite systemic administration of adjuvant chemotherapy. Many assume that this is because the majority of DTCs are quies...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/s41556-018-0267-0
更新日期:2019-02-01 00:00:00
abstract::Tissue stem cells are the cell of origin for many malignancies. Metabolites regulate the balance between self-renewal and differentiation, but whether endogenous metabolic pathways or nutrient availability predispose stem cells towards transformation remains unknown. Here, we address this question in epidermal stem ce...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/s41556-020-0525-9
更新日期:2020-07-01 00:00:00
abstract::While nuclear lamina abnormalities are hallmarks of human diseases, their interplay with epigenetic regulators and precise epigenetic landscape remain poorly understood. Here, we show that loss of the lysine acetyltransferase MOF or its associated NSL-complex members KANSL2 or KANSL3 leads to a stochastic accumulation...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/s41556-019-0397-z
更新日期:2019-10-01 00:00:00
abstract::Dozens of proteins capture, polymerize and reshape the clathrin lattice during clathrin-mediated endocytosis (CME). How or if this ensemble of proteins is organized in relation to the clathrin coat is unknown. Here, we map key molecules involved in CME at the nanoscale using correlative super-resolution light and tran...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb3498
更新日期:2017-04-01 00:00:00
abstract::We describe a genome-wide gain-of-function screen for regulators of NF-kappaB, and identify Rap1 (Trf2IP), as an essential modulator of NF-kappaB-mediated pathways. NF-kappaB is induced by ectopic expression of Rap1, whereas its activity is inhibited by Rap1 depletion. In addition to localizing on telomeres, mammalian...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb2080
更新日期:2010-08-01 00:00:00
abstract::The promyelocytic leukaemia (PML) tumour-suppressor protein potentiates p53 function by regulating post-translational modifications, such as CBP-dependent acetylation and Chk2-dependent phosphorylation, in the PML-Nuclear Body (NB). PML was recently shown to interact with the p53 ubiquitin-ligase Mdm2 (refs 4-6); howe...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb1147
更新日期:2004-07-01 00:00:00
abstract::Accurate chromosome segregation during cell division in metazoans relies on proper chromosome congression at the equator. Chromosome congression is achieved after bi-orientation to both spindle poles shortly after nuclear envelope breakdown, or by the coordinated action of motor proteins that slide misaligned chromoso...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb3060
更新日期:2014-12-01 00:00:00
abstract::We have identified Rab10 as an ER-specific Rab GTPase that regulates ER structure and dynamics. We show that Rab10 localizes to the ER and to dynamic ER-associated structures that track along microtubules and mark the position of new ER tubule growth. Rab10 depletion or expression of a Rab10 GDP-locked mutant alters E...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb2647
更新日期:2013-02-01 00:00:00
abstract::Inhibitors of apoptosis (IAPs) inhibit caspases, thereby preventing proteolysis of apoptotic substrates. IAPs occlude the active sites of caspases to which they are bound and can function as ubiquitin ligases. IAPs are also reported to ubiquitinate themselves and caspases. Several proteins induce apoptosis, at least i...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb798
更新日期:2002-06-01 00:00:00
abstract::Proteins containing ubiquitin-binding domains (UBDs) interact with ubiquitinated targets and regulate diverse biological processes, including endocytosis, signal transduction, transcription and DNA repair. Many of the UBD-containing proteins are also themselves monoubiquitinated, but the functional role and the mechan...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb1354
更新日期:2006-02-01 00:00:00
abstract::Actin networks drive many essential cellular processes, including cell migration, cytokinesis and tissue morphogenesis. However, how cells organize and regulate dynamic actin networks that consist of long, unbranched actin filaments is only poorly understood. This study in mouse oocytes reveals that cells can use vesi...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb2802
更新日期:2013-08-01 00:00:00
abstract::Blocking mitotic progression has been proposed as an attractive therapeutic strategy to impair proliferation of tumour cells. However, how cells survive during prolonged mitotic arrest is not well understood. We show here that survival during mitotic arrest is affected by the special energetic requirements of mitotic ...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb3231
更新日期:2015-10-01 00:00:00
abstract::The motion of a chromosome during mitosis is mediated by a bundle of microtubules, termed a kinetochore fibre (K-fibre), which connects the kinetochore of the chromosome to a spindle pole. Once formed, mature K-fibres maintain a steady state length because the continuous addition of microtubule subunits onto microtubu...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb1207
更新日期:2005-01-01 00:00:00
abstract::Many extracellular signals are transmitted to the interior of the cell by receptors with seven membrane-spanning helices that trigger their effects by means of heterotrimeric guanine-nucleotide-binding regulatory proteins (G proteins). These G-protein-coupled receptors (GPCRs) control various physiological functions i...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb1133
更新日期:2004-06-01 00:00:00
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
更新日期:2000-05-01 00:00:00
abstract::Loss-of-function (LOF) mutations in the endothelial cell (EC)-enriched gene endoglin (ENG) cause the human disease hereditary haemorrhagic telangiectasia-1, characterized by vascular malformations promoted by vascular endothelial growth factor A (VEGFA). How ENG deficiency alters EC behaviour to trigger these anomalie...
journal_title:Nature cell biology
pub_type: 杂志文章
doi:10.1038/ncb3534
更新日期:2017-06-01 00:00:00