Abstract:
:Pyroptosis is a form of cell death that is critical for immunity. It can be induced by the canonical caspase-1 inflammasomes or by activation of caspase-4, -5 and -11 by cytosolic lipopolysaccharide. The caspases cleave gasdermin D (GSDMD) in its middle linker to release autoinhibition on its gasdermin-N domain, which executes pyroptosis via its pore-forming activity. GSDMD belongs to a gasdermin family that shares the pore-forming domain. The functions and mechanisms of activation of other gasdermins are unknown. Here we show that GSDME, which was originally identified as DFNA5 (deafness, autosomal dominant 5), can switch caspase-3-mediated apoptosis induced by TNF or chemotherapy drugs to pyroptosis. GSDME was specifically cleaved by caspase-3 in its linker, generating a GSDME-N fragment that perforates membranes and thereby induces pyroptosis. After chemotherapy, cleavage of GSDME by caspase-3 induced pyroptosis in certain GSDME-expressing cancer cells. GSDME was silenced in most cancer cells but expressed in many normal tissues. Human primary cells exhibited GSDME-dependent pyroptosis upon activation of caspase-3 by chemotherapy drugs. Gsdme-/- (also known as Dfna5-/-) mice were protected from chemotherapy-induced tissue damage and weight loss. These findings suggest that caspase-3 activation can trigger necrosis by cleaving GSDME and offer new insights into cancer chemotherapy.
journal_name
Naturejournal_title
Natureauthors
Wang Y,Gao W,Shi X,Ding J,Liu W,He H,Wang K,Shao Fdoi
10.1038/nature22393subject
Has Abstractpub_date
2017-07-06 00:00:00pages
99-103issue
7661eissn
0028-0836issn
1476-4687pii
nature22393journal_volume
547pub_type
杂志文章相关文献
NATURE文献大全abstract::Amyloid beta-protein (AP) is a peptide of relative molecular mass (Mr) 42,000 found in the senile plaques, cerebrovascular amyloid deposits, and neurofibrillary tangles of patients with Alzheimer's disease and Down's syndrome (trisomy 21). Recent molecular genetic evidence has indicated that AP is encoded as part of a...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/329156a0
更新日期:1987-09-10 00:00:00
abstract::Three environmental groups have filed suit against the National Institutes of Health in an attempt to block an experiment approved in April by the NIH Recombinant DNA Advisory Committee. The experiment, designed by researchers at the University of California, Berkeley, to enhance the frost resistance of crops, would ...
journal_title:Nature
pub_type: 新闻
doi:10.1038/305262a0
更新日期:1983-09-22 00:00:00
abstract::In the course of synaptic transmission in the brain and periphery, acetylcholine receptors (AChRs) rapidly transduce a chemical signal into an electrical impulse. The speed of transduction is facilitated by rapid ACh association and dissociation, suggesting a binding site relatively non-selective for small cations. Se...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature07923
更新日期:2009-05-21 00:00:00
abstract::Calcium (Ca(2+))-activated chloride channels are fundamental mediators in numerous physiological processes including transepithelial secretion, cardiac and neuronal excitation, sensory transduction, smooth muscle contraction and fertilization. Despite their physiological importance, their molecular identity has remain...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature07313
更新日期:2008-10-30 00:00:00
abstract::Interchromosomal gene conversion between alleles has been shown in yeast frequently to be associated with the recombination of flanking genetic markers. Although this also holds true for gene conversion between two alleles of the yeast mating-type (MAT) locus, initiated by the homothallic switching system, we find no ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/310744a0
更新日期:1984-08-30 00:00:00
abstract::The Tasmanian devil, a large carnivorous Australian marsupial, is under threat from a widespread fatal disease in which a malignant oral-facial tumour obstructs the animal's ability to feed. Here we show that the chromosomes in these tumours have undergone a complex rearrangement that is identical for every animal stu...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/439549a
更新日期:2006-02-02 00:00:00
abstract::Materials showing simultaneous ferroelectric and magnetic ordering are attracting a great deal of interest because of their unusual physics and potential applications. Hemberger et al. have reported relaxor-like dielectric properties and colossal magnetocapacitance (in excess of 500%) for the cubic spinel compound CdC...
journal_title:Nature
pub_type: 评论,杂志文章
doi:10.1038/nature06156
更新日期:2007-08-23 00:00:00
abstract::Glycogen synthase kinase-3beta (GSK-3beta) has integral roles in a variety of biological processes, including development, diabetes, and the progression of Alzheimer's disease. As such, a thorough understanding of GSK-3beta function will have a broad impact on human biology and therapeutics. Because GSK-3beta interact...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature05557
更新日期:2007-03-01 00:00:00
abstract::Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per a...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature21039
更新日期:2017-02-09 00:00:00
abstract::Global patterns of species richness and their structuring forces have fascinated biologists since Darwin and provide critical context for contemporary studies in ecology, evolution and conservation. Anthropogenic impacts and the need for systematic conservation planning have further motivated the analysis of diversity...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature09329
更新日期:2010-08-26 00:00:00
abstract::Glycosaminoglycans such as heparan sulphate and chondroitin sulphate are extracellular sugar chains involved in intercellular signalling. Disruptions of genes encoding enzymes that mediate glycosaminoglycan biosynthesis have severe consequences in Drosophila and mice. Mutations in the Drosophila gene sugarless, which ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature01635
更新日期:2003-05-22 00:00:00
abstract::The B cells of the immune system, which secrete antibodies against foreign antigens, are fully specific and effective only after maturation in lymph nodes and other lymphoid tissues. Immunocompetent T cells play a crucial part in this process, but the molecular details of the way in which the two cell types interact h...
journal_title:Nature
pub_type: 杂志文章,评审
doi:10.1038/367425a0
更新日期:1994-02-03 00:00:00
abstract::Calcium signalling in astrocytes couples changes in neural activity to alterations in cerebral blood flow by eliciting vasoconstriction or vasodilation of arterioles. However, the mechanism for how these opposite astrocyte influences provide appropriate changes in vessel tone within an environment that has dynamic met...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature07525
更新日期:2008-12-11 00:00:00
abstract:: ...
journal_title:Nature
pub_type: 评论,社论
doi:10.1038/d41586-019-00483-5
更新日期:2019-02-01 00:00:00
abstract::Recent studies have shown that initial sensitization to airborne environmental allergens occurs typically in early childhood, but subsequent progression to persistent atopic asthma, which may not manifest for several years, is restricted to only a subset of atopics. The key to establishing the link between atopy and a...
journal_title:Nature
pub_type: 杂志文章,评审
doi:10.1038/35037009
更新日期:1999-11-25 00:00:00
abstract::Mammalian cells proteolytically release (shed) the extracellular domains of many cell-surface proteins. Modification of the cell surface in this way can alter the cell's responsiveness to its environment and release potent soluble regulatory factors. The release of soluble tumour-necrosis factor-alpha (TNF-alpha) from...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/385729a0
更新日期:1997-02-20 00:00:00
abstract::An extensive repertoire of modifications is known to underlie the versatile coding, structural and catalytic functions of RNA, but it remains largely uncharted territory. Although biochemical studies indicate that N(6)-methyladenosine (m(6)A) is the most prevalent internal modification in messenger RNA, an in-depth st...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature11112
更新日期:2012-04-29 00:00:00
abstract::The availability of methods for the amplification of nucleic acid sequences allows the genetic analysis in vitro of the structural and functional properties of many nucleic acids. We have now developed an in vitro selection and amplification system, and used it to analyse the self-splicing Tetrahymena ribozyme. A much...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/347406a0
更新日期:1990-09-27 00:00:00
abstract::COPII-coated vesicles form on the endoplasmic reticulum by the stepwise recruitment of three cytosolic components: Sar1-GTP to initiate coat formation, Sec23/24 heterodimer to select SNARE and cargo molecules, and Sec13/31 to induce coat polymerization and membrane deformation. Crystallographic analysis of the Sacchar...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature01040
更新日期:2002-09-19 00:00:00
abstract::Several microorganisms, including Yersinia sp., Salmonella sp., Brucella sp., Mycobacterium sp. and Leishmania sp., have successfully adapted to grow within macrophage phagolysosomes. Infections caused by these intracellular pathogens are among the most difficult to treat. As part of an antimicrobial strategy directed...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/322834a0
更新日期:1986-08-28 00:00:00
abstract::A magnetic field penetrates a superconductor through an array of 'vortices', each of which carries one quantum of flux that is surrounded by a circulating supercurrent. In this vortex state, the resistivity is determined by the dynamical properties of the vortex 'matter'. For the high-temperature copper oxide supercon...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35078016
更新日期:2001-05-24 00:00:00
abstract::Exchange dynamics between molecules free in solution and bound to the surface of a large supramolecular structure, a polymer, a membrane or solid support are important in many phenomena in biology and materials science. Here we present a novel and generally applicable solution NMR technique, known as dark-state exchan...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature10577
更新日期:2011-10-30 00:00:00
abstract::The E6 oncoprotein derived from tumour-associated human papillomaviruses (HPVs) binds to and induces the degradation of the cellular tumour-suppressor protein p53. A common polymorphism that occurs in the p53 amino-acid sequence results in the presence of either a proline or an arginine at position 72. The effect of t...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/30400
更新日期:1998-05-21 00:00:00
abstract::Recent studies have demonstrated that monkeys and humans can use signals from the brain to guide computer cursors. Brain-computer interfaces (BCIs) may one day assist patients suffering from neurological injury or disease, but relatively low system performance remains a major obstacle. In fact, the speed and accuracy ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature04968
更新日期:2006-07-13 00:00:00
abstract::Non-small-cell lung cancer is the leading cause of cancer-related death worldwide. Chemotherapies such as the topoisomerase II (TopoII) inhibitor etoposide effectively reduce disease in a minority of patients with this cancer; therefore, alternative drug targets, including epigenetic enzymes, are under consideration f...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature14122
更新日期:2015-04-09 00:00:00
abstract::The widely occurring tetradecapeptide somatostatin (SRIF-14) has been variously implicated as a neurotransmitter, a neurohormone, a cybernin (local regulatory factor) and a hormone. In the first isolation of SRIF-14 from hypothalamic extracts and subsequent extracts of other tissues, peptides of higher molecular weigh...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/291076a0
更新日期:1981-05-07 00:00:00
abstract::In somatic cells, entry into mitosis depends on the completion of DNA synthesis. This dependency is established by S-phase feedback controls that arrest cell division when damaged or unreplicated DNA is present. In the fission yeast Schizosaccharomyces pombe, mutations that interfere with the phosphorylation of tyrosi...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/355365a0
更新日期:1992-01-23 00:00:00
abstract::Proximal spinal muscular atrophies represent the second most common fatal, autosomal recessive disorder after cystic fibrosis. The childhood form is classically subdivided into three groups: acute Werdnig-Hoffmann (type I), intermediate Werdnig-Hoffmann disease (type II) and Kugelberg-Welander disease (type III). Thes...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/344767a0
更新日期:1990-04-19 00:00:00
abstract::Nature's high-performance polymer, spider silk, consists of specific proteins, spidroins, with repetitive segments flanked by conserved non-repetitive domains. Spidroins are stored as a highly concentrated fluid dope. On silk formation, intermolecular interactions between repeat regions are established that provide st...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature08962
更新日期:2010-05-13 00:00:00
abstract::Soybean (Glycine max (L.) Merr.) is an important crop that provides a sustainable source of protein and oil worldwide. Soybean cyst nematode (Heterodera glycines Ichinohe) is a microscopic roundworm that feeds on the roots of soybean and is a major constraint to soybean production. This nematode causes more than US$1 ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature11651
更新日期:2012-12-13 00:00:00