Volume 12 Issue 1, January 2011

Volume 12 Issue 1

Members of the PARP superfamily regulate many biological and pathological cellular responses. Takaoka and colleagues identify the PARP-13 shorter isoform ZAPS as a potent stimulator of RNA helicase RIG-I-mediated signaling during viral infection (p 37; News and Views by Gale Jr, p 11). The original pseudocolor-based image of corrected FRET shows an interaction between YFP-tagged ZAPS and CFP-tagged RIG-I. Original image by Fumi Kashigi and Yusuke Ohba. Artwork by Lewis Long.

Editorial

  • Editorial |

    Against a backdrop of some of the most savage spending cuts in the developed world, the UK science budget has emerged relatively unscathed, but funding priorities may yet prove problematic.

Correspondence

Commentary

  • Commentary |

    The fields of immunology, microbiology, nutrition and metabolism are rapidly converging. Here we expand on a diet-microbiota model as the basis for the greater incidence of asthma and autoimmunity in developed countries.

    • Kendle M Maslowski
    •  & Charles R Mackay

News and Views

  • News & Views |

    ZAPS, a member of the poly(ADP-ribose) polymerase family, modulates innate antiviral immunity by boosting signaling of the RNA helicase RIG-I.

    • Helene Minyi Liu
    •  & Michael Gale Jr
  • News & Views |

    NF-κB is a critical transcription factor that is regulated by several post-transcriptional modifications. The characterization of their roles would help in the design of new therapeutic targets in cancer and inflammation.

    • Jorge Moscat
    •  & Maria T Diaz-Meco
  • News & Views |

    The molecular mechanisms that control Treg and TH17 development and the precise role of TGF-β in this process are complex and imperfectly understood. New findings indicate that the helix-loop-helix proteins E2A and Id3 are also critically involved in some of these processes.

    • Masahide Tone
    •  & Mark I Greene
  • News & Views |

    TH2 cells control immune responses to helminth infection and contribute to the development of allergic asthma. A single intronic enhancer element in Il4 can regulate TH2 differentiation and susceptibility to allergic asthma via interaction with the transcription factor GATA-3.

    • Melanie Van Stry
    •  & Mark Bix

Research Highlights

Review

Articles

  • Article |

    Binding of the transcription factor NF-κB subunit RelA activates proinflammatory gene expression. Gozani and colleagues show that basal expression of RelA target genes is suppressed by methylation of RelA by SETD6, which triggers repressive histone methylation by GLP.

    • Dan Levy
    • , Alex J Kuo
    • , Yanqi Chang
    • , Uwe Schaefer
    • , Christopher Kitson
    • , Peggie Cheung
    • , Alexsandra Espejo
    • , Barry M Zee
    • , Chih Long Liu
    • , Stephanie Tangsombatvisit
    • , Ruth I Tennen
    • , Andrew Y Kuo
    • , Song Tanjing
    • , Regina Cheung
    • , Katrin F Chua
    • , Paul J Utz
    • , Xiaobing Shi
    • , Rab K Prinjha
    • , Kevin Lee
    • , Benjamin A Garcia
    • , Mark T Bedford
    • , Alexander Tarakhovsky
    • , Xiaodong Cheng
    •  & Or Gozani
  • Article |

    Poly(ADP-ribose) polymerases participate in many biological and pathological processes. Takaoka and co-workers show that the short isoform of PARP-13 (ZAPS) is selectively induced by 5'-triphosphate–modified RNA and regulates signaling mediated by the RNA helicase RIG-I.

    • Sumio Hayakawa
    • , Souichi Shiratori
    • , Hiroaki Yamato
    • , Takeshi Kameyama
    • , Chihiro Kitatsuji
    • , Fumi Kashigi
    • , Showhey Goto
    • , Shoichiro Kameoka
    • , Daisuke Fujikura
    • , Taisho Yamada
    • , Tatsuaki Mizutani
    • , Mika Kazumata
    • , Maiko Sato
    • , Junji Tanaka
    • , Masahiro Asaka
    • , Yusuke Ohba
    • , Tadaaki Miyazaki
    • , Masahiro Imamura
    •  & Akinori Takaoka
  • Article |

    Peptides presented to cytotoxic T lymphocytes are typically generated by proteasome action. Kessler and colleagues show that the cytosolic endopeptidases nardilysin and thimet oligopeptidase generate the C termini of tumor-relevant epitopes.

    • Jan H Kessler
    • , Selina Khan
    • , Ulrike Seifert
    • , Sylvie Le Gall
    • , K Martin Chow
    • , Annette Paschen
    • , Sandra A Bres-Vloemans
    • , Arnoud de Ru
    • , Nadine van Montfoort
    • , Kees L M C Franken
    • , Willemien E Benckhuijsen
    • , Jill M Brooks
    • , Thorbald van Hall
    • , Kallol Ray
    • , Arend Mulder
    • , Ilias I N Doxiadis
    • , Paul F van Swieten
    • , Hermen S Overkleeft
    • , Annik Prat
    • , Birgitta Tomkinson
    • , Jacques Neefjes
    • , Peter M Kloetzel
    • , David W Rodgers
    • , Louis B Hersh
    • , Jan W Drijfhout
    • , Peter A van Veelen
    • , Ferry Ossendorp
    •  & Cornelis J M Melief
  • Article |

    HLA-DM activity ensures that only high-affinity peptides are displayed on MHC class II molecules. Wucherpfennig and colleagues show that interaction of HLA-DR with the N terminus of bound peptides determines susceptibility to HLA-DM.

    • Anne-Kathrin Anders
    • , Melissa J Call
    • , Monika-Sarah E D Schulze
    • , Kevin D Fowler
    • , David A Schubert
    • , Nilufer P Seth
    • , Eric J Sundberg
    •  & Kai W Wucherpfennig
  • Article |

    Immunoglobulin genes are prominent targets of the deaminase AID. Casellas and Nussenzweig and co-workers show that whereas stalled polymerases recruit AID across the B cell genome, efficient hypermutation is restricted to immunoglobulin loci by the RPA cofactor of AID.

    • Arito Yamane
    • , Wolfgang Resch
    • , Nan Kuo
    • , Stefan Kuchen
    • , Zhiyu Li
    • , Hong-wei Sun
    • , Davide F Robbiani
    • , Kevin McBride
    • , Michel C Nussenzweig
    •  & Rafael Casellas
  • Article |

    Immunoglobulin genes are further diversified by the cytidine deaminase AID. Gearhart and colleagues show immunoglobulin genes accumulate AID-dependent uracil residues within the first 24 hours of B cell stimulation.

    • Robert W Maul
    • , Huseyin Saribasak
    • , Stella A Martomo
    • , Rhonda L McClure
    • , William Yang
    • , Alexandra Vaisman
    • , Hillary S Gramlich
    • , David G Schatz
    • , Roger Woodgate
    • , David M Wilson III
    •  & Patricia J Gearhart
  • Article |

    The molecular basis of TH2 lineage commitment is poorly understood. Kubo and colleagues identify the Il4 enhancer HS2 as a target of the transcription factor GATA-3 and show it to be critical for IL-4 production and TH2 functional commitment.

    • Shinya Tanaka
    • , Yasutaka Motomura
    • , Yoshie Suzuki
    • , Ryoji Yagi
    • , Hiromasa Inoue
    • , Shoichiro Miyatake
    •  & Masato Kubo
  • Article |

    TGF-β and Foxp3 are required for the development of regulatory T cells. Chen and colleagues show that the helix-loop-helix proteins E2A and Id3 enhance Foxp3 expression and relieve it from inhibition by other transcription factors.

    • Takashi Maruyama
    • , Jun Li
    • , Jose P Vaque
    • , Joanne E Konkel
    • , Weifeng Wang
    • , Baojun Zhang
    • , Pin Zhang
    • , Brian F Zamarron
    • , Dongyang Yu
    • , Yuntao Wu
    • , Yuan Zhuang
    • , J Silvio Gutkind
    •  & WanJun Chen
  • Article |

    Transcription factors specific for helper T cell lineages, such as T-bet, counter-regulate helper T cell development, but the details of this remain unclear. Glimcher and colleagues unravel the molecular basis of the regulation of TH17 cells by T-bet.

    • Vanja Lazarevic
    • , Xi Chen
    • , Jae-Hyuck Shim
    • , Eun-Sook Hwang
    • , Eunjung Jang
    • , Alexandra N Bolm
    • , Mohamed Oukka
    • , Vijay K Kuchroo
    •  & Laurie H Glimcher