Apoptosis articles within Nature Communications

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  • Article
    | Open Access

    Calcium flux must be carefully controlled during the phagocytosis of apoptotic cells (efferocytosis), although how this occurs is not fully understood. Here, the authors show that the Cereblon E3 ligase regulates Orai1 degradation and subsequently SOCE-mediated calcium influx.

    • Hyunji Moon
    • , Chanhyuk Min
    •  & Daeho Park

  • Article
    | Open Access

    Mandibuloacral dysplasias (MADs) are rare progeroid syndromes characterized by nuclear morphological and functional abnormalities. Here the authors report that loss of mitochondrial membrane protein MTX2 causes a progeroid MAD sharing clinical features with lamin-associated progeroid syndromes.

    • Sahar Elouej
    • , Karim Harhouri
    •  & Annachiara De Sandre-Giovannoli

  • Article
    | Open Access

    Mitochondrial apoptosis is controlled by BCL2 family proteins, and the BH3-only proteins often act as sensors that transmit apoptotic signals. Here the authors show how the BH3-only proteins BMF and HRK can directly activate the BCL2 protein BAK and interact with BAK through an alternative binding groove.

    • Kaiqin Ye
    • , Wei X. Meng
    •  & Haiming Dai

  • Article
    | Open Access

    PDE3A modulators for cancer therapy cause serious side effects as they inhibit PDE3A phosphodiesterase activity, which is essential for the maturation of oocytes and the formation of platelets. Here, the authors identify a compound, nauclefine, that does not inhibit PDE3A activity but induces apoptosis by enabling a complex formation between PDE3A and SLFN12.

    • Youwei Ai
    • , Haibing He
    •  & Xiangbing Qi

  • Article
    | Open Access

    Cell competition among epithelial cells allows removal of unfit or dangerous cells. Here, the authors show that the NMDA receptor is an important determinant of cell fitness in the Drosophila wing, also in the context of Myc super-competitor cells, with “loser” cells contributing metabolitic fuel to “winner” cells.

    • Agnes R. Banreti
    •  & Pascal Meier

  • Article
    | Open Access

    Codon 158 gain-of-function mutant p53 (158-mutp53) promotes tumourigenesis in lung cancer. Here, the authors show that 158-mutp53 render cancers sensitive to cisplatin and p53 acetylation agents through a mechanism where acetylated mutant p53 upregulates TRAIP and inhibits NF-ĸB signaling.

    • Li Ren Kong
    • , Richard Weijie Ong
    •  & Boon Cher Goh

  • Article
    | Open Access

    Receptor interacting protein kinase 1 (RIPK1) regulates cell death and inflammatory responses. Here the authors show that autophosphorylation at Ser166 is required for RIPK1-mediated cell death and inflammation in mouse models of inflammatory pathologies, making Ser166 phosphorylation a possible biomarker for RIPK1-mediated inflammatory diseases.

    • Lucie Laurien
    • , Masahiro Nagata
    •  & Manolis Pasparakis

  • Article
    | Open Access

    Yamanaka factors can reprogram somatic and cancer cells into induced pluripotent stem cells. Here, the authors show that the induction of these factors in acute myeloid leukemia leads to apoptosis of leukemia cells in vivo, and this is through modulation of chromatin accessibility to apoptotic genes and accompanied by H3K9me3 dysregulation.

    • Yajie Wang
    • , Ting Lu
    •  & Tao Cheng

  • Article
    | Open Access

    Cancer cells utilise the unfolded protein response (UPR) to adapt to environmental and ER stress. Here, the authors show that the glycosidase II beta subunit, PRKSCH, protects cancer cells from ER stress, by interacting with IRE1α and activating the IRE1α-XBP1 branch of the UPR.

    • Gu-Choul Shin
    • , Sung Ung Moon
    •  & Kyun-Hwan Kim

  • Article
    | Open Access

    In inflammasomes, caspase-1 activation leads to pyroptosis mediated by gasdermin D, but cells lacking gasdermin-D still initiate caspase-dependent cell death. Here, Tsuchiya et al. show that these cells undergo Bid- and caspase-3-dependent apoptosis.

    • Kohsuke Tsuchiya
    • , Shinsuke Nakajima
    •  & Takashi Suda

  • Article
    | Open Access

    Cerebral Cavernous Malformations (CCM) are often caused by mutations in CCM1/KRIT1. Here, Chapman et al. elegantly show that the CCM complex promotes apoptosis by regulating zinc homeostasis and storage via a conserved mechanism that likely generates the pathological defects observed in CCM.

    • Eric M. Chapman
    • , Benjamin Lant
    •  & W. Brent Derry

  • Article
    | Open Access

    BAX and BAK are pro-apoptotic proteins whose activity is essential for the action of many anti-cancer drugs and to suppress tumorigenesis. Here, the authors perform a genome-wide CRISPR/Cas9 screen and identify VDAC2 as a promoter of BAX-mediated apoptosis that is important for an efficient chemotherapeutic response and to suppress tumor formation.

    • Hui San Chin
    • , Mark X. Li
    •  & Grant Dewson

  • Article
    | Open Access

    The mechanisms regulating intestinal stem cell elimination remain unclear. Here, the authors identify that the pro-apoptotic protein ARTS (a Septin4 isoform) interacts with XIAP in the intestinal stem cell niche to  regulate stem cell survival during intestinal homeostasis and regeneration.

    • Elle Koren
    • , Yahav Yosefzon
    •  & Yaron Fuchs

  • Article
    | Open Access

    TNF mediated inflammation is critical in autoimmune mediated pathology, however many patients are refractory to current anti-TNF therapeutics. Here the authors show induction of several death ligands, in addition to TNF is sufficient to cause fatal dermatitis in a LUBAC deficient murine model of disease.

    • Lucia Taraborrelli
    • , Nieves Peltzer
    •  & Henning Walczak

  • Article
    | Open Access

    Gliotoxin (GT), produced by the pulmonary pathogen A. fumigatus, induces detachment-induced apoptosis (anoikis) of lung epithelial cells and likely promotes invasion. Here, the authors show that GT covalently modifies integrins at the RGD binding site followed by activation of RhoA-ROCK-MKK4/7-JNK signalling leading to Bim-mediated anoikis.

    • Florian Haun
    • , Simon Neumann
    •  & Christoph Borner

  • Article
    | Open Access

    Dependency of diverse cancers on specific BCL-2 family members and their combinations is unknown. Here they perform drug screening and find most cell lines to be dependent on at least one combination of BCL-2 family members, and using a CRISPR screen find BCL-w and BFL-1 to mediate resistance to BH3 mimetics

    • Ryan S. Soderquist
    • , Lorin Crawford
    •  & Kris C. Wood

  • Article
    | Open Access

    Erythropoietin (EPO) stimulates erythropoiesis and is commonly used to treat anemia. Here Hu et al. find that P38α/JNK signaling restrains erythropoiesis independently of EPO by regulating epigenetic silencing of the proapoptotic protein Bim, and thus identify putative targets for the treatment of anemic disorders resistant to EPO.

    • Ping Hu
    • , Angel R. Nebreda
    •  & Reuben Kapur

  • Article
    | Open Access

    The inhibitor of apoptosis (IAP) protein, BRUCE is known to ubiquitinate apoptosis regulators for proteasomal degradation. Here the authors show that BRUCE provides a bridge between LAMP2 on lysosomes and Atg8 family proteins on autophagosomes to support autophagosome-lysosome fusion.

    • Petra Ebner
    • , Isabella Poetsch
    •  & Fumiyo Ikeda

  • Article
    | Open Access

    The Tetraconata concept suggests that insects and crustaceans may share evolutionarily conserved pathways. Here, the authors describe the animal tropism and structure-function relationship of nigritoxin, showing that this protein is lethal for insects and crustaceans but harmless to other animals.

    • Yannick Labreuche
    • , Sabine Chenivesse
    •  & Frédérique Le Roux

  • Article
    | Open Access

    Bcl-2 interacting killer (Bik) decreases airway epithelial hyperplasia via apoptosis mediated by calcium release from the endoplasmic reticulum (ER), but the mechanism is unclear. Here the authors show that Bik promotes Bak enrichment at the ER to tether mitochondria for efficient calcium transfer.

    • Yohannes A. Mebratu
    • , Ivan Leyva-Baca
    •  & Yohannes Tesfaigzi

  • Article
    | Open Access

    High-grade serous ovarian cancers (HGS-OvCa) frequently develop chemotherapy resistance. Here, the authors through a systematic analysis of proteomic and drug response data of 14 HGS-OvCa PDXs demonstrate that targeting apoptosis regulators can improve response of these tumors to inhibitors of the PI3K/mTOR pathway.

    • Ioannis K. Zervantonakis
    • , Claudia Iavarone
    •  & Joan S. Brugge

  • Article
    | Open Access

    Notch signalling is deregulated in several cancers; therefore, strategies targeting this pathway are currently being explored. Here the authors report a pro-apoptotic function of Notch3 in endothelial cells; consequently, when Notch3 is silenced in stroma cells, tumour growth and angiogenesis are increased.

    • Shuheng Lin
    • , Ana Negulescu
    •  & Patrick Mehlen

  • Article
    | Open Access

    Small cell lung cancer cells (SCLC) are differentially sensitive to inhibitors of the BCL-2 family. Here the authors analyse the response to BH3 mimetics in SCLC, delineate patterns of expression of apoptotic proteins correlated with differential sensitivities and demonstrate a synergistic anti-tumour activity between ABT-199 and anthracyclines or CDK9 inhibitors.

    • Akane Inoue-Yamauchi
    • , Paul S. Jeng
    •  & Emily H. Cheng

  • Article
    | Open Access

    The permeabilization of the mitochondrial outer membrane to induce apoptosis is regulated by complex interactions between Bcl-2 family members. Here the authors develop a quantitative interactome of a membrane Bcl-2 network and identify a hierarchy of protein complexes in apoptosis induction.

    • Stephanie Bleicken
    • , Annika Hantusch
    •  & Ana J. Garcia-Saez

  • Article
    | Open Access

    Spatiotemporal control of intracellular molecular self-assembly holds promise for therapeutic applications. Here the authors develop a peptide consisting of a phenylalanine dipeptide with a mitochondrial targeting moiety to form self-assembling fibrous nanostructures within mitochondria, leading to apoptosis.

    • M. T. Jeena
    • , L. Palanikumar
    •  & Ja-Hyoung Ryu

  • Article
    | Open Access

    Investigating cell death in living organisms is hampered by a lack of techniques to induce apoptosis with spatial and temporal precision without collateral damage. Here the authors develop two-photon chemical apoptotic targeted ablation (2Phatal), allowing studies of apoptosis and its functional consequencesin vivo.

    • Robert A. Hill
    • , Eyiyemisi C. Damisah
    •  & Jaime Grutzendler

  • Article
    | Open Access

    The exocyst delivers basolateral proteins from the secretory pathway to the plasma membrane of epithelial cells close to tight junctions. Here the authors show that Par3 acts as a docking site for the exocyst to regulate polarized delivery of basolateral proteins and this is essential to prevent apoptosis and promote mammary cell survival.

    • Syed Mukhtar Ahmed
    •  & Ian G. Macara

  • Article
    | Open Access

    The kinase FAK is important for integrin signalling and promotes cell survival. Here, the authors demonstrate FAK regulates adipocyte survival, and is particularly important for maintaining insulin sensitivity during adipose tissue expansion in the context of a calorie-rich diet.

    • Cynthia T. Luk
    • , Sally Yu Shi
    •  & Minna Woo

  • Article
    | Open Access

    DFNA5 is related to the caspase-dependent pyroptosis inducer gasdermin D. Here the authors find that DFNA5 is cleaved by caspase 3 and show this cleavage skews cells away from apoptosis into secondary necrosis, a form of cell death characterized by membrane ballooning similar to pyroptosis.

    • Corey Rogers
    • , Teresa Fernandes-Alnemri
    •  & Emad S. Alnemri

  • Article
    | Open Access

    The tumour microenvironment can be modulated to sensitize tumours to the effects of therapy. Here the authors show that radiation induced miR-103 downregulates TREX1 in endothelial cells, decreases angiogenesis and leads to the secretion of proinflammatory mediators that reduce tumour growth.

    • RaeAnna Wilson
    • , Cristina Espinosa-Diez
    •  & Sudarshan Anand

  • Article
    | Open Access

    Diabetes is characterized by prolonged hyperglycaemia and tissue damage in pancreatic islets. Here, Brereton et al. show that chronic high glucose levels lead to glycogen accumulation in β-cells, associated with reduced autophagy, impaired metabolism, insulin granule depletion and apoptosis.

    • Melissa F. Brereton
    • , Maria Rohm
    •  & Frances M. Ashcroft

  • Article
    | Open Access

    Rela is a transcription factor shown to have seemingly contradictory roles in anabolism and catabolism of cartilage. Here the authors find that Rela prevents chondrocyte apoptosis and that homozygous knockout causes accelerated osteoarthritis in adults, whereas heterozygous knockout suppresses osteoarthritis by maintaining wild-type effects on apoptosis but inhibiting catabolic gene expression.

    • Hiroshi Kobayashi
    • , Song Ho Chang
    •  & Taku Saito

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