Post-translational modifications articles within Nature

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  • Letter |

    Genome-wide analysis shows that H2B S112 O-linked to N-acetylglucosamine is frequently located near transcribed genes, suggesting that histone GlcNAcylation facilitates transcription of the genes.

    • Ryoji Fujiki
    • , Waka Hashiba
    •  & Shigeaki Kato

  • Letter |

    The ubiquitin conjugation system regulates the canonical NF-κB-activation pathway, which mediates immune responses. Linear polyubiquitin chains—in which the C-terminal glycine of ubiquitin is conjugated to the α-amino group of the amino-terminal methionine of another ubiquitin—are generated by a unique ubiquitin ligase complex called linear ubiquitin chain assembly complex (LUBAC) composed of two RING domain proteins called HOIL-1 and HOIP. This is one of three complementary studies identifying a novel component of the LUBAC complex called SHARPIN, which is recruited to receptor signalling complexes (RSCs) that form after TNF and CD40L stimulation. The LUBAC complex containing SHARPIN stimulates the formation of linear ubiquitin chains in vitro and in vivo and is required for the activation of NF-κB signalling.

    • Fuminori Tokunaga
    • , Tomoko Nakagawa
    •  & Kazuhiro Iwai

  • Article |

    The presence of DNA lesions is a clear signal that initiates the DNA damage response; however, the mechanisms that attenuate this response when repair has occurred are less clear. Here, deacetylation of Sae2 by Rpd3 and Hda1 is shown to be required for it to act on Mre11. When the role of Sae2 in resection is completed, it is acetylated by Gcn5 and degraded through an autophagic pathway. This work highlights links between DNA damage signalling, acetylation of repair factors, and autophagy mediated degradation of these factors.

    • Thomas Robert
    • , Fabio Vanoli
    •  & Marco Foiani

  • Letter |

    Activating AMPK or inactivating calcineurin slows ageing in worms and increases their lifespan. Here it is shown that inhibition of CRTC-1 is required for these life-extending effects. CRTC-1 is the only worm member in the family of CREB-regulated transcriptional co-activators, or CRTCs, and, like the mammalian family members, CRTC-1 interacts with a worm homologue of the CREB transcription factor (CRH-1). Eliminating crtc-1 increases lifespan in a crh-1-dependent manner, as does elimination of crh-1 alone. Downregulation of components in the CRTC/CREB pathway has previously been shown to confer health benefits to mice, complementing their lifespan effects in worms.

    • William Mair
    • , Ianessa Morantte
    •  & Andrew Dillin

  • News & Views |

    Protein factors can regulate gene expression by binding to specifically modified DNA-associated proteins. Small molecules that selectively interfere with such interaction may be of therapeutic value. See Article p.1067 & Letter p.1119

    • Sean D. Taverna
    •  & PhiliP A. Cole

  • Letter |

    Ubiquitination of histone H2A has been implicated in polycomb-mediated transcriptional silencing, but its precise functions are unclear. Here, ZRF1 is shown to be recruited to ubiquitinated H2A and to function in displacing polycomb-repressive complex 1 (PRC1) from chromatin to facilitate transcriptional activation.

    • Holger Richly
    • , Luciana Rocha-Viegas
    •  & Luciano Di Croce

  • Letter |

    These authors identify the human enzyme responsible for menaquinone-4 biosynthesis, a naturally occurring form of vitamin K. They find that UbiA prenyltransferase containing 1, a human homologue of a prenyltransferase gene from Escherichia coli, encodes an enzyme that can convert vitamin K derivatives into menaquinone-4.

    • Kimie Nakagawa
    • , Yoshihisa Hirota
    •  & Toshio Okano

  • Letter |

    Two classes of enzyme — cyclin-dependent kinases (CDK) and Dbf4-dependent kinase (DDK) — facilitate the initiation of DNA replication in eukaryotes. It is now shown that, when DNA damage is sensed, another kinase, Rad53, halts the firing of late replication origins by inhibiting both the CDK and the DDK pathways. Rad53 acts on DDK directly by inhibiting Dbf4, whereas the CDK pathway is blocked by Rad53-mediated phosphorylation of the downstream CDK substrate Sld3.

    • Jaime Lopez-Mosqueda
    • , Nancy L. Maas
    •  & David P. Toczyski

  • Letter |

    Two classes of enzyme — cyclin-dependent kinases (CDK) and Dbf4-dependent kinase (DDK) — facilitate the initiation of DNA replication in eukaryotes. It is now shown that, when DNA damage is sensed, another kinase, Rad53, halts the firing of late replication origins by inhibiting both the CDK and the DDK pathways. Rad53 acts on DDK directly by inhibiting Dbf4, whereas the CDK pathway is blocked by Rad53-mediated phosphorylation of the downstream CDK substrate Sld3.

    • Philip Zegerman
    •  & John F. X. Diffley

  • Letter |

    The chromosomal passenger complex (CPC) coordinates several processes during cell division, including chromosome bi-orientation and cytokinesis, and its proper localization is crucial. These authors provide a mechanism for its localization to the inner centromere. Cdk1–cyclin-B-dependent phosphorylation of the CPC promotes binding to shugoshin, which the authors define as a conserved centromeric adaptor of the CPC. This mechanism is conserved between fission yeast and human cells and highlights a crucial role of Cdk1–cyclin B in chromosome bi-orientation.

    • Tatsuya Tsukahara
    • , Yuji Tanno
    •  & Yoshinori Watanabe

  • Article |

    When double-strand breaks occur in eukaryotic DNA, the chromatin that protects and organizes the genome must be removed from the vicinity of the break to allow repair factors to bind. Such chromatin displacement involves the addition of ubiquitin groups to histone proteins near the break by the ubiquitin ligases RNF8 and RNF168. Here it is shown that the enzyme OTUB1 prevents RNF168-dependent poly-ubiquitination. Pharmacological targeting of this process might enhance the DNA damage response.

    • Shinichiro Nakada
    • , Ikue Tai
    •  & Daniel Durocher

  • Letter |

    The initiation of protein synthesis requires the eukaryotic translation initiation factor (eIF) 2, which uses energy from the hydrolysis of GTP. Another factor, eIF5, accelerates the GTP-hydrolysing activity of eIF2. Here, two other roles for eIF5 have been defined. One involves stabilizing GDP, the product of GTP hydrolysis, on eIF2. In its other role, eIF5 works with phosphorylated eIF2 to inhibit the guanine-nucleotide exchange factor eIF2B. These results clarify our understanding of how the initiation of translation is regulated.

    • Martin D. Jennings
    •  & Graham D. Pavitt

  • Letter |

    SUMOylation is a post-translational protein modification that affects many eukaryotic cellular processes. It is shown here that cellular infection with Listeria monocytogenes induces degradation of one of the essential SUMOylation enzymes, Ubc9, through a mechanism that involves a bacterial toxin, listeriolysin O. This effect on SUMOylation may support efficient infection by Listeria.

    • David Ribet
    • , Mélanie Hamon
    •  & Pascale Cossart

  • Letter |

    The amino-terminal tails of histone proteins are subject to a variety of post-translational modifications; addition or removal of these 'marks' facilitates gene activation or silencing. Here, a mechanism is defined that modulates the activity of the dual-specificity histone demethylase LSD1 during androgen-dependent transcription. Androgen-dependent signalling through protein kinase C beta I leads to phosphorylation of a histone amino acid, which prevents demethylation of an adjacent amino acid by LSD1.

    • Eric Metzger
    • , Axel Imhof
    •  & Roland Schüle

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