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Volume 14 Issue 6, June 2012

MYC inhibits cell migration, invasion and metastasis by suppressing the expression of integrin αv and β3 subunits, which are needed for these processes.p567

Editorial

  • As the pace of translational stem cell research accelerates, researchers and governing bodies must work together to develop and implement rigorous ethical standards to guide the transition into the clinical sphere.

    Editorial

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Turning Points

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News & Views

  • The diverse nature of eukaryotic centromere structure has led to a prevailing view that the kinetochore–chromatin interface is fundamentally different in distinct species. Two studies now challenge this dogma with the identification of budding yeast homologues of the vertebrate centromere DNA-binding proteins CENP-T and CENP-W.

    • Karen E. Gascoigne
    • Iain M. Cheeseman
    News & Views
  • The Ndc80 complex links spindle microtubules to the kinetochore to ensure the proper segregation of chromosomes during mitosis. Analysis of the replication licensing factor Cdt1 during mitosis now reveals a cooperative role with the Ndc80 complex in establishing stable microtubule attachments to the spindle.

    • Daniel R. Matson
    • P. Todd Stukenberg
    News & Views
  • Bcl-2 family proteins are known to control cell death and influence mitochondrial function. The function of Mcl-1, an anti-apoptotic Bcl-2 protein, is now shown to depend on its subcellular localization. Mcl-1 at the mitochondrial outer membrane inhibits mitochondrial permeabilization to block apoptosis. However, a cleaved form of Mcl-1 localizes to the mitochondrial matrix and controls inner mitochondrial morphology and oxidative phosphorylation, without directly modulating apoptosis.

    • Joshua L. Andersen
    • Sally Kornbluth
    News & Views
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Research Highlights

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Article

  • Radisky and colleagues show that, in contrast to its pro-tumorigenic properties, the MYC oncogene is also able to inhibit metastasis by suppressing cell migration and invasiveness. Mechanistically, they show that MYC transcriptionally represses the integrin αv and β3 subunits, which are needed for efficient cell motility and invasion.

    • Hong Liu
    • Derek C. Radisky
    • J. Michael Bishop
    Article
  • MCL-1 is an anti-apoptotic BCL-2 family member and is frequently upregulated in cancer, but the mechanism by which it promotes cell survival has been elusive. Opferman and colleagues provide insight into this process by showing that MCL-1 exists in different forms with discrete localizations and functions. MCL-1 variants targeted to the outer mitochondrial membrane antagonize BAX and BAK activation, whereas an N-terminally truncated isoform localizes to the mitochondrial matrix and regulates mitochondrial metabolism.

    • Rhonda M. Perciavalle
    • Daniel P. Stewart
    • Joseph T. Opferman
    Article
  • Integrin internalization through the endosomal pathway can lead either to recycling back to the surface or to lysosomal degradation. Faessler and colleagues now show that, following internalization, β1 integrins are bound by sorting nexin 17 in early endosomes to prevent integrin degradation in lysosomes and to promote surface recycling.

    • Ralph Thomas Böttcher
    • Christopher Stremmel
    • Reinhard Fässler
    Article
  • Multi-protein kinetochore complexes bind to the centromeric region of chromosomes to ensure accurate spindle attachment and chromosome segregation, although centromere organization differs widely between species. Westermann and colleagues now identify the budding yeast protein Cnn1 as the orthologue of mammalian CENP-T. They show that it binds to the Ndc80 kinetochore complex and functions in chromosome segregation, illustrating a conserved role for this protein.

    • Alexander Schleiffer
    • Michael Maier
    • Stefan Westermann
    Article
  • The kinetochore is a multiprotein complex that tethers chromosomes to the mitotic spindle for accurate chromosome segregation. De Wulf and colleagues now show in budding yeast that the protein Cnn1 functions at the kinetochore and is recruited to the inner kinetochore, in a manner dependent on its phosphorylation mediated by the Cdc28, Mps1 and Ipl1 kinases.

    • Lucy J. Bock
    • Cinzia Pagliuca
    • Peter De Wulf
    Article
  • Mak and colleagues report that TRADD, an adaptor protein important in tumour necrosis factor receptor (TNFR) signalling, contributes to tumour suppression independently of TNFR. They show that nuclear TRADD binds to the tumour suppressor p19Arf and inhibits its interaction with the E3 ubiquitin ligase ULF, leading to p19Arf stability and promoting cell senescence.

    • Iok In Christine Chio
    • Masato Sasaki
    • Tak Wah Mak
    Article
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Letter

  • Clathrin-mediated endocytosis requires the generation of membrane curvature and subsequent formation of clathrin-coated vesicles. Using a cell-free system, Dannhauser and Ungewickell show that clathrin polymerization is capable of inducing membrane deformation and generating spherical vesicles.

    • Philip N. Dannhauser
    • Ernst J. Ungewickell
    Letter
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Resource

  • Wedlich-Söldner and colleagues characterize the localization of plasma membrane proteins in Saccharomyces cerevisiae by total internal reflection microscopy and deconvolution. Their data reveal a self-organization of proteins into patterns and demonstrate that association of the arginine transporter Can1 with its membrane domain is important for its function.

    • Felix Spira
    • Nikola S. Mueller
    • Roland Wedlich-Söldner
    Resource
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Erratum

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Corrigendum

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