Apoptosis articles within Nature Communications

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  • Article
    | Open Access

    Integrins are transmembrane proteins that have important roles in cell adhesion and signalling. Here the authors design a therapeutic protein that binds integrin αvβ3, has anti-angiogenic activity, and reduces tumour growth in xenograft models, while being seemingly well tolerated.

    • Ravi Chakra Turaga
    • , Lu Yin
    •  & Zhi-Ren Liu

  • Article
    | Open Access

    The transcription factor CHOP/GADD153 regulates apoptosis in response to the unfolded protein response. Here the authors show that CHOP/GADD153 regulates the expression of miR-216b, which targets c-Jun and sensitizes cells to ER stress-dependent apoptosis.

    • Zhenhua Xu
    • , Yiwen Bu
    •  & J. Alan Diehl

  • Article
    | Open Access

    Apoptosis often requires mitochondrial outer membrane permeabilization, a process targeted by Bcl-2-binding BH3 mimetics. Here the authors describe and apply 'mito-priming', a method that allows triggering mitochondrial apoptosis in a synchronous manner, facilitating the investigation of mitochondrial apoptosis and its regulation by Bcl-2 proteins.

    • Jonathan Lopez
    • , Margaux Bessou
    •  & Stephen W. G. Tait

  • Article
    | Open Access

    Proteinuria promotes chronic kidney disease progression. Karoui et al. show that proteinuria stimulates overexpression of iron transporting protein lipocalin-2 via Ca2+release-induced ER stress, which leads to tubular apoptosis, and that inhibition of this pathway by PBA delays renal deterioration in proteinuric mice.

    • Khalil El Karoui
    • , Amandine Viau
    •  & Fabiola Terzi

  • Article
    | Open Access

    Cytoplasmic stress granules (SG) are intracellular aggregates that suppress translation and sequester apoptosis regulatory factors. Here the authors show that reactive oxygen species oxidise the SG-nucleating protein TIA1, preventing SG formation and promoting apoptosis in the presence of additional stress.

    • Kyoko Arimoto-Matsuzaki
    • , Haruo Saito
    •  & Mutsuhiro Takekawa

  • Article
    | Open Access

    Several histone modifiers have been implicated in the survival of multiple myeloma cells. Here, the authors reveal a role for the histone demethylase KDM3A in the survival of this haematologic cancer, and show that mechanistically KDM3A removes H3K9 methylation from the promoters of KLF2 and IRF4, genes essential for myeloma cell survival.

    • Hiroto Ohguchi
    • , Teru Hideshima
    •  & Kenneth C. Anderson

  • Article |

    Slow-dividing ‘loser’ cells are outcompeted by more robust ‘winner’ cells and eliminated by macrophage-like haemocytes in the fruit fly larva. Here the authors show that the dying loser cells secrete the enzyme Tyrosyl-tRNA synthetase that upon Mmp2-mediated cleavage acts as a haemocyte chemoattractant.

    • Sergio Casas-Tintó
    • , Fidel-Nicolás Lolo
    •  & Eduardo Moreno

  • Article
    | Open Access

    Programed cell death occurs in a stereotypic fashion duringC. elegansdevelopment, and it is thought that engulfment promotes programmed cell death. Here the authors present evidence that a signaling function of the conserved engulfment pathways, not the process of engulfment itself, promotes apoptotic cell death.

    • Sayantan Chakraborty
    • , Eric J. Lambie
    •  & Barbara Conradt

  • Article
    | Open Access

    The proapoptotic protein Bax triggers cell death by forming pores in the outer mitochondrial membrane. Using single-particle TIRF imaging, the authors show that Bax binds the membrane in a monomeric state before forming dimers and multimers of dimers, which are disassembled by the survival protein Bcl-xL.

    • Yamunadevi Subburaj
    • , Katia Cosentino
    •  & Ana J. García-Sáez

  • Article
    | Open Access

    Tumour cells can survive by evading cell death pathways and altering their metabolism to adapt to their local environment. In this study, Iansanteet al. show that the anti-apoptotic protein PARP14 maintains low PKM2 activity, leading to enhanced glycolysis, demonstrating a link between suppression of apoptosis and altered metabolism.

    • Valeria Iansante
    • , Pui Man Choy
    •  & Salvatore Papa

  • Article
    | Open Access

    ER stress is associated with the pathogenesis of chronic kidney disease (CKD) and new CKD therapies are needed. Here the authors show that expression of Rtn1 can control severity of renal disease and that inhibition of its expression can attenuate ER stress and CKD.

    • Ying Fan
    • , Wenzhen Xiao
    •  & John C. He

  • Article
    | Open Access

    Reprogramming holds great promise for regenerative medicine but the molecular mechanisms governing the generation of induced pluripotent stem cells remain unclear. Here, the authors reveal functions for the axonal guidance cue Netrin-1 in constraining apoptosis at the early stage of reprogramming and in established pluripotent cells.

    • Duygu Ozmadenci
    • , Olivier Féraud
    •  & Fabrice Lavial

  • Article
    | Open Access

    CENP-E regulates chromosome alignment during mitosis to distribute chromosomes equally into daughter cells. Here, the authors show that CENP-E inhibition causes p53-mediated post-mitotic apoptosis in tumours where the spindle assembly checkpoint is compromised, suggesting that CENP-E is a therapeutic target for these cancers.

    • Akihiro Ohashi
    • , Momoko Ohori
    •  & Kentaro Iwata

  • Article
    | Open Access

    KDEL receptors are known to be involved in retrotransporting chaperones to the endoplasmic reticulum from the Golgi complex. Here the authors unravel a role of KDEL receptor 1 in regulating integrated stress responses in naïve T cells through its association with protein phosphatase 1.

    • Daisuke Kamimura
    • , Kokichi Katsunuma
    •  & Masaaki Murakami

  • Article |

    Ovarian cancer is often accompanied by metastases at the time of diagnosis and has a poor survival rate. In this study, Aslan et al.identify a role for ZNF304 in ovarian cancer metastasis and show that the protein transcriptionally regulates β1 integrin, resulting in a reduction in programmed cell death.

    • Burcu Aslan
    • , Paloma Monroig
    •  & Gabriel Lopez-Berestein

  • Article
    | Open Access

    The tumour suppressor p53 is known to be inhibited by histone deacetylase 3 but the molecular mechanism is poorly understood. Here Choi et al. show regulation by programmed cell death 5 and an essential role in activating p53 following DNA damage.

    • Hyo-Kyoung Choi
    • , Youngsok Choi
    •  & Ho-Geun Yoon

  • Article
    | Open Access

    During apoptosis, cells break up into smaller fragments to facilitate removal. Here the authors characterize a beads-on-a-string structure formed by monocytes undergoing apoptosis in vitro, which shears into apoptotic bodies lacking nuclear contents, and is blocked by the antidepressant sertraline.

    • Georgia K. Atkin-Smith
    • , Rochelle Tixeira
    •  & Ivan K.H. Poon

  • Article |

    Some normal and cancer stem cells are resistant to killing by genotoxins, but the mechanism for this resistance is poorly understood. Here the authors show that adult stem cells inDrosophila melanogastergermline and midgut are resistant to genotoxic stimuli and find that this is mediated by signalling via the receptor tyrosine kinase Tie released from apoptotic cells.

    • Yalan Xing
    • , Tin Tin Su
    •  & Hannele Ruohola-Baker

  • Article
    | Open Access

    Cellular functions of the vault complex, a large ribonucleoprotein assembly remain elusive. Here, the authors show that Epstein–Barr virus infection enhances the expression of the vault complex-associated RNAs, which leads to improved survival of infected cells due to the inhibition of cell apoptosis.

    • Melanie Amort
    • , Birgit Nachbauer
    •  & Norbert Polacek

  • Article
    | Open Access

    Cells experiencing extended mitotic arrest often undergo cell death as a result of steadily declining levels of the apoptotic inhibitor MCL1, but the mechanism controlling this process is poorly understood. Here, Haschka et al.show that the BH3-only protein NOXA promotes the degradation of MCL1, enabling BIM-dependent cell death.

    • Manuel D. Haschka
    • , Claudia Soratroi
    •  & Luca L. Fava

  • Article |

    During apoptosis, Bak undergoes major conformational changes that lead to mitochondrial permeabilization. Here, the authors characterize changes that occur within the Bak N-terminus using a series of antibodies and a novel tethering approach, demonstrating that dissociation of the α1 helix is a key early step in the unfolding of Bak.

    • Amber E. Alsop
    • , Stephanie C. Fennell
    •  & Ruth M. Kluck

  • Article |

    Nonsense-mediated mRNA decay (NMD) is a pathway that controls endogenous transcript levels and limits the production of aberrant mRNAs. Here the authors show that NMD is attenuated in cells treated with chemotherapeutic compounds through caspase-mediated proteolytic cleavage of UPF1, a key NMD effector.

    • Maximilian W. Popp
    •  & Lynne E. Maquat

  • Article |

    The poly(ADP-ribose) polymerase PARP13 targets RNA viruses by binding to viral RNA and promoting its degradation by cellular decay factors such as the exosome. Todorova et al. find that PARP13 also plays a much broader role as a regulator of host mRNA stability, and promotes apoptosis by degrading TRAILR4transcripts.

    • Tanya Todorova
    • , Florian J. Bock
    •  & Paul Chang

  • Article |

    The transcription factor Wilms’ tumour 1 (WT1) regulates kidney development, and Wt1 mutations are associated with renal cancer. Here the authors identify WT1 target genes in renal progenitors during early kidney development in mouse embryos and show that loss of Wt1suppresses FGF and induces BMP signalling.

    • Fariba Jian Motamedi
    • , Danielle A. Badro
    •  & Andreas Schedl

  • Article |

    The pRb target E2F1 possesses contradictory activities in promoting proliferation and apoptosis. Here, the authors define a pRb-Skp2-p27-cyclin A-E2F1 survival pathway that can be disrupted to prevent Rb1-deficient tumorigenesis in the pituitary intermediate lobe.

    • Zhonglei Lu
    • , Frederick Bauzon
    •  & Liang Zhu

  • Article |

    In the early stages of atherosclerosis, macrophages in the vessel wall convert into foam cells, which promote the rise of atherosclerotic plaques. Here Hamada et al. show that the macrophage transcription factor MafB inhibits foam-cell apoptosis, and that its absence promotes atherosclerosis development in mice.

    • Michito Hamada
    • , Megumi Nakamura
    •  & Satoru Takahashi

  • Article |

    Cells in Drosophila salivary glands undergo hormone-dependent apoptosis when larvae pupate. Here, the authors show that the histone methylase dUTX regulates activation of key cell death and autophagy genes leading to the removal of salivary glands during the Drosophilalarval–pupal transition.

    • Donna Denton
    • , May T. Aung-Htut
    •  & Sharad Kumar

  • Article |

    Pellino family proteins are ubiquitin ligases known to regulate immune signalling. Here Yang et al. show that Pellino3 regulates apoptotic TNF signalling by modulating the composition of the death-induced signalling complex, and that absence of Pellino3 sensitizes mice to TNF.

    • Shuo Yang
    • , Bingwei Wang
    •  & Paul N. Moynagh

  • Article |

    Recent studies suggest that there is an overlap between neuronal apoptosis and axon-specific degeneration. Cusack and colleagues show that the caspase-dependent pathways mediating axon degeneration during apoptosis are distinct from those mediating localized axon pruning.

    • Corey L. Cusack
    • , Vijay Swahari
    •  & Mohanish Deshmukh

  • Article |

    The protein ataxia-telangiectasia mutated (ATM) detects DNA damage and can trigger cellular apoptosis, but how this process is regulated at the molecular level is unclear. Here, Chunget al. show that the transcription factor FOXO3 controls the formation of ATM-containing signalling complexes at sites of DNA damage that trigger apoptosis.

    • Young Min Chung
    • , See-Hyoung Park
    •  & Mickey C.-T. Hu

  • Article |

    Abnormal mitochondrial fission leads to apoptosis and disease. Li and colleagues reveal the mechanism with which the transcription factor Foxo3a suppresses Fis1-mediated mitochondrial fission and apoptosis in cardiomyocytes and adrenocortical cancer cells, which involves miR-484 inhibition of Fis1 translation.

    • Kun Wang
    • , Bo Long
    •  & Pei-Feng Li

  • Article
    | Open Access

    The control of cell fate and apoptosis is a continuing challenge in synthetic biology. In this study, systems are developed in which an intracellularly expressed genome-encoded protein simultaneously achieves up- and downregulation of two distinct apoptosis pathways.

    • Hirohide Saito
    • , Yoshihiko Fujita
    •  & Tan Inoue

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