Volume 12 Issue 3, March 2010

Volume 12 Issue 3

Hedgehog activation in interfollicular epidermis progenitors leads to basal cell carcinoma. [letter p299]

Editorial

  • Editorial |

    A shared culture of science across nations can bring cohesion in the face of difference. The launch of the Nature Middle East portal promises to engage the Arabic-speaking science community.

Turning Points

News and Views

  • News & Views |

    Peroxisomes can import large multimeric protein complexes and even 9-nm gold particles decorated with peroxisome-targeting signals. They achieve these feats of protein passage using a distinctive translocon whose highly dynamic aqueous pore can expand to accommodate the increasing girths of different peroxisome receptor–cargo complexes.

    • Fred D. Mast
    • , Andrei Fagarasanu
    •  & Richard Rachubinski
  • News & Views |

    Bone remodelling in vertebrates is coordinately regulated by the opposing effects of parathyroid hormone (PTH) and transforming growth factor-beta (TGF-β). PTH couples the processes of bone resorption and formation by enforcing simultaneous internalization of TGF-β type II receptor (TβRII) and PTH type 1 receptor (PTH1R), which attenuates both TGF-β and PTH signalling in vivo.

    • Azeddine Atfi
    •  & Roland Baron
  • News & Views |

    The p62 protein recognizes toxic cellular waste, which is then scavenged by a sequestration process known as self-eating or autophagy. Lack of autophagy leads to accumulation of p62, which is not good for liver cells, as it induces a cellular stress response that leads to disease.

    • Tor Erik Rusten
    •  & Harald Stenmark
  • News & Views |

    The microRNA miR-9 is induced by Myc in breast cancer cells where it targets the major epithelial adherens junction protein, E-cadherin. This primes the cancer cells for epithelial–mesenchymal transition (EMT) and also stimulates angiogenesis in tumours.

    • Yeesim Khew-Goodall
    •  & Gregory J. Goodall

Research Highlights

  • Research Highlights |

    • Emily Chenette
    • , Nathalie Le Bot
    • , Christina Karlsson Rosenthal
    •  & Sowmya Swaminathan

Articles

  • Article |

    Impaired turnover of the autophagy substrate p62 leads to liver injury. p62 inhibits the ubiquitin ligase Keap1, leading to stabilization of the transcription factor Nrf2. High levels of p62 in autophagy deficient animals leads to unusually high expression of Nrf2 targets genes and results in liver injury.

    • Masaaki Komatsu
    • , Hirofumi Kurokawa
    • , Satoshi Waguri
    • , Keiko Taguchi
    • , Akira Kobayashi
    • , Yoshinobu Ichimura
    • , Yu-Shin Sou
    • , Izumi Ueno
    • , Ayako Sakamoto
    • , Kit I. Tong
    • , Mihee Kim
    • , Yasumasa Nishito
    • , Shun-ichiro Iemura
    • , Tohru Natsume
    • , Takashi Ueno
    • , Eiki Kominami
    • , Hozumi Motohashi
    • , Keiji Tanaka
    •  & Masayuki Yamamoto
  • Article |

    In response to parathyroid hormone (PTH), TGF-β type II receptor (TβRII) directly phosphorylates the PTH type I receptor (PTH1R) and modulates PTH-induced endocytosis of a PTH1R/TβRII complex. Mice that lack TβRII display higher bone mass — a phenotype similar to that observed in mice expressing a constitutively active version of PTH1R.

    • Tao Qiu
    • , Xiangwei Wu
    • , Fengjie Zhang
    • , Thomas L. Clemens
    • , Mei Wan
    •  & Xu Cao
  • Article |

    A prostate cancer epigenome map reveals that genes are suppressed in clusters through long-range epigenetic silencing (LRES). Regions of LRES contain known tumour suppressors and miRNAs, and may expand to neighbouring genes during tumour progression.

    • Marcel W. Coolen
    • , Clare Stirzaker
    • , Jenny Z. Song
    • , Aaron L. Statham
    • , Zena Kassir
    • , Carlos S. Moreno
    • , Andrew N. Young
    • , Vijay Varma
    • , Terence P. Speed
    • , Mark Cowley
    • , Paul Lacaze
    • , Warren Kaplan
    • , Mark D. Robinson
    •  & Susan J. Clark
  • Article |

    miRNAs can both promote and repress tumorigenesis, and directly control epithelial–mesenchymal transition (EMT). miR-9 (which is upregulated in breast cancer cells) is activated by MYC and MYCN, and regulates EMT and metastasis through direct control of E-cadherin. In contrast, tumour angiogenesis is controlled indirectly through effects on vascular endothelial growth factor (VEGF) expression.

    • Li Ma
    • , Jennifer Young
    • , Harsha Prabhala
    • , Elizabeth Pan
    • , Pieter Mestdagh
    • , Daniel Muth
    • , Julie Teruya-Feldstein
    • , Ferenc Reinhardt
    • , Tamer T. Onder
    • , Scott Valastyan
    • , Frank Westermann
    • , Frank Speleman
    • , Jo Vandesompele
    •  & Robert A. Weinberg
  • Article |

    In postnatal skeletal muscle, satellite cells are resident myogenic progenitors responsible for muscle growth and regeneration. A distinct population of muscle-resident stem cells that localizes in the interstitium and expresses the factor PW1 is identified. These cells are myogenic and contribute to muscle regeneration in vivo.

    • Kathryn J. Mitchell
    • , Alice Pannérec
    • , Bruno Cadot
    • , Ara Parlakian
    • , Vanessa Besson
    • , Edgar R. Gomes
    • , Giovanna Marazzi
    •  & David A. Sassoon

Letters

  • Letter |

    PTP1B, an ER-localized tyrosine phosphatase, regulates signalling by various cell-surface receptors, including epidermal growth factor receptor (EGFR). Direct contacts between EGFR-containing endosomes and the ER allow EGFR and PTP1B to interact. PTP1B promotes sorting of EGFR into multivesicular bodies.

    • Emily R. Eden
    • , Ian J. White
    • , Anna Tsapara
    •  & Clare E. Futter
  • Letter |

    It remains unclear how proteins translocate across the peroxisomal membrane. Insights into a potential import pore are provided with the finding that the import receptor Pex5p forms a dynamic ion channel together with Pex14p, which can be induced to open upon receptor-cargo complex association.

    • Michael Meinecke
    • , Christian Cizmowski
    • , Wolfgang Schliebs
    • , Vivien Krüger
    • , Sabrina Beck
    • , Richard Wagner
    •  & Ralf Erdmann
  • Letter |

    Notch-mediated transcriptional activation requires the formation of a ternary complex, consisting of NotchICD, CSL and a Mastermind family member. Nemo-like kinase is shown to negatively regulate Notch signalling and to promote neurogenesis in zebrafish by phosphoprylating Notch1ICD and reducing formation of the ternary complex.

    • Tohru Ishitani
    • , Tomoko Hirao
    • , Maho Suzuki
    • , Miho Isoda
    • , Shizuka Ishitani
    • , Kenichi Harigaya
    • , Motoo Kitagawa
    • , Kunihiro Matsumoto
    •  & Motoyuki Itoh
  • Letter |

    A post-transcriptional pathway mediates TGFbeta-induced epithelial–mesenchymal transition (EMT). TGFβ-activated Akt phosphorylates the heterogeneous ribonucleoprotein E1, releasing it from the 3′-UTR of two transcripts required for EMT: disabled-2 (Dab2) and interleukin-like EMT inducer (ILEI).

    • Arindam Chaudhury
    • , George S. Hussey
    • , Partho S Ray
    • , Ge Jin
    • , Paul L. Fox
    •  & Philip H. Howe
  • Letter |

    Cells at the origin of tumour initiation are unknown for many cancers. In hedgehog-induced basal cell carcinoma, skin hair-follicle stem cells do not participate to tumorigenesis, whereas Hedgehog activation in stem cells from the interfollicular epidermis does induce malignancy.

    • Khalil Kass Youssef
    • , Alexandra Van Keymeulen
    • , Gäelle Lapouge
    • , Benjamin Beck
    • , Cindy Michaux
    • , Younes Achouri
    • , Panagiota A. Sotiropoulou
    •  & Cédric Blanpain

Corrigenda