Research Highlights

Short, accessible synopses of recent important articles concerning signalling pathways.

December 2006

• DNA damage: The road of death

  

  DNA damage activates checkpoint pathways that induce cell-cycle arrest and subsequent DNA repair or cell death. Cyclin-dependent kinase-2 (CDK2) is inhibited by DNA damage, but whether CDK2 has a role in DNA-damage-induced cell death has been unknown. Donald Tindall and colleagues have addressed this question and found that CDK2-mediated phosphorylation of the transcription factor FOXO1 regulates apoptosis following DNA damage.

  Original research paper Nature Reviews Molecular Cell Biology 7 878 - 879 doi:10.1038/nrm2073

• The potential of networking

  

  Embryonic stem (ES) cells are singled out by their pluripotent potential, a property that is fostered by the homeodomain protein Nanog. Reporting in Nature, Stuart Orkin and colleagues now reveal the complex network of proteins that work together with Nanog to maintain the developmental options of ES cells.

  Original research paper Nature Reviews Molecular Cell Biology 7 881 doi:10.1038/nrm2071

• Bioenergetics: Turn up the heat

  

  PGC1 transcriptional co-activators are important regulators of mitochondrial biogenesis and respiration. Two new studies from the Spiegelman laboratory now shed light on the role of PGC1 in several disease aetiologies. PGC1 and PGC1 are implicated in oxidative-damage-related neurodegeneration by suppressing the generation of reactive oxygen species (ROS). Moreover, PGC1 is associated with defective energy homeostasis associated with Leigh syndrome French Canadian variant (LSFC), a genetic disorder that is characterized by neurodegeneration and severe liver defects.

  Original research paper Nature Reviews Molecular Cell Biology 7 883 doi:10.1038/nrm2070

• Expanding the pathway

  

  Since its discovery there has been much interest in the Salvador–Warts–Hippo (Sav–Wts–Hpo) growth-regulating pathway, which was first described in Drosophila melanogaster and is conserved in humans. Three groups, led by Georg Halder, Kieran Harvey, and Helen McNeill and Nick Tapon, have identified the atypical cadherin Fat as an upstream regulator of this pathway.

  Original research paper Nature Reviews Molecular Cell Biology 7 709 doi:10.1038/nrm2035

• Contract and move

  

  The regulated assembly and disassembly of cell–extracellular matrix junctions (focal adhesions) contributes to cell motility and tumour invasion. Rho–ROCK signalling promotes focal adhesion disassembly at the rear of the cell by inducing contractile forces that are dependent on the phosphorylation of myosin light chain 2 (MLC2). Isacke and colleagues now show that the Rho–ROCK–MLC2 signalling pathway is activated to generate contractile forces at distinct subcellular locations through endosomal trafficking.

  Original research paper Nature Reviews Molecular Cell Biology 7 706 - 707 doi:10.1038/nrm2032

• Polar architecture disrupted

  

  Epithelial organization is often disrupted during the development of carcinomas. Although several oncogenes have been shown to alter the localization of polarity markers in epithelial cells, the mechanisms by which this occurs are unclear. Senthil Muthuswamy and colleagues now show that the oncogenic receptor tyrosine kinase ERBB2 (also known as HER2) disrupts polarized epithelial cell organization by associating with components of the Par polarity complex.

  Original research paper Nature Reviews Molecular Cell Biology 7 705 doi:10.1038/nrm2033

• Rooting out resistance

  

  Glioblastomas are aggressive brain tumours that rapidly become resistant to radiotherapy. Jeremy Rich and colleagues now show that glioma stem cells are the root of this problem.

  Original research paper Nature Reviews Molecular Cell Biology 7 792 doi:10.1038/nrm2051