Reviews & Analysis

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  • A crucial aspect of cell function in tissues is the biophysical interactions of the cell with the surrounding extracellular matrix. A fascinating report in this issue offers a major advance in the techniques available for investigating how the transmission of cell-generated forces to an underlying substratum is regulated. Application of this approach should provide key insights into such force regulation during cell migration and matrix contraction.

    • Douglas A. Lauffenburger
    • Alan Wells
    News & Views
  • For almost a century, our understanding of the tiny structure at the centre of the cell called the centrosome was limited to its ability to organize mitotic spindles and other microtubule arrays. However, recent studies have indicated new roles for centrosomes in cytokinesis and cell-cycle progression.

    • Stephen J. Doxsey
    News & Views
  • Although membrane blebbing is a characteristic morphological change associated with apoptosis, little is known about the mechanisms underlying this process. New research has identified the Rho GTPase target ROCK-I as being cleaved by caspases during apoptosis. ROCK-I is known to stimulate actomyosin-based contractility. Once cleaved, ROCK-I is constitutively active and is responsible for bleb formation in apoptotic cells.

    • Yann Leverrier
    • Anne J. Ridley
    News & Views
  • Spinal muscular atrophy is caused by mutations in the survival motor neurons gene, SMN1. The SMN protein localizes to both the cytoplasm and the nuclear bodies. One hallmark of spinal muscular atrophy is the failure of SMN to localize within these nuclear bodies. A recent study has identified a protein called ZPR1 that is required for nuclear translocation of SMN.

    • A. Gregory Matera
    • Michael D. Hebert
    News & Views
  • Recent work has discovered the role of the cyclin-dependent kinase (CDK)-binding protein Cks1 in degrading the CDK inhibitor p27Kip1. This process is essential for DNA replication and is aberrantly enhanced in cancer. Surprisingly, new work indicates that this function of Cks1 is independent of CDKs and links Cks1 with the Skp2 subunit of the SCF ubiquitin ligase.

    • Jiri Bartek
    • Jiri Lukas
    News & Views
  • Recent work in Drosophila has shown that the adherens junctions of epithelial cells provide a planar cue to orientate mitotic spindles during symmetrical division. This planar cue depends on the function of E-APC and dEB1, homologues of the adenomatous polyposis coli (APC) tumour suppressor and of the microtubule-binding yeast protein Bim1.

    • Mariann Bienz
    News & Views
  • The identification of proteins that are important for microtubule nucleation, regulation of microtubule dynamics and spindle assembly has been an exciting area of research. A series of recent papers have now provided key insights into these processes by identifying downstream targets of Ran that result in aster formation and spindle assembly.

    • Claire E. Walczak
    News & Views
  • The universal cell-cycle inhibitor p21Cip1/WAF1 is phosphorylated and localized in the cytoplasm in Her2/neu-overexpressing breast cancers as a result of its physical association with the oncogenic Akt protein. Subcellular mislocalization of checkpoint controllers is now surfacing as a mechanism of deregulating cell proliferation in cancer.

    • Wafik S. El-Deiry
    News & Views
  • The Arp2/3 complex affects the rate of actin polymerization and promotes cellular actin assembly. Recent work has shown that cortactin is capable of stimulating the actin-nucleating activity of the Arp2/3 complex. In addition, more insight has been gained into how new actin-filament branches are formed and how actin patches in yeast are assembled.

    • Markus Zettl
    • Michael Way
    News & Views
  • Recent work has clarified how higher eukaryotic cells 'licence' DNA replication precisely once per cycle. An inhibitor, geminin, prevents replication before mitosis by inhibiting the replication factor Cdt1. Degradation of geminin in anaphase allows Cdt1 to promote binding of MCM proteins, and hence DNA replication.

    • Mark Madine
    • Ron Laskey
    News & Views
  • Molecular chaperones have long been heralded as machines for folding and salvaging proteins. However, not every attempt to fold or refold a protein can be successful. Chaperones are known to participate in the degradation of misfolded polypeptides, but a direct link between folding and degradation pathways has remained elusive. Two recent reports show that the co-chaperone CHIP mediates ubiquitin-dependent degradation of substrates bound to heat-shock protein 70 (Hsp70) and/or Hsp90.

    • Amie J. McClellan
    • Judith Frydman
    News & Views
  • Chemokines are generally appreciated within the realm of immunology as chemoattractant cytokines that are involved in constitutive and inducible movement of white blood cells. However, evidence increasingly points to a broader function of chemokines in cellular and developmental biology, and the initially T-associated chemokine RANTES has now been shown to produce age-dependent effects on developing human astrocytes.

    • Craig Gerard
    • Norma P. Gerard
    News & Views