Research Highlights

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

March 2007

• Signalling pathways: Collusion

  

  Approximately 25% of breast cancers overexpress the protein tyrosine kinase ERBB2, and their dependence on its expression has been verified through the clinical success of the anti-ERBB2 antibody trastuzumab. However, single agents are often at risk of driving the selection of resistant clones, and Michel L. Tremblay and colleagues have found that inhibition of the protein tyrosine phosphatase PTPN1 (also known as PTP1B) could improve anti-ERBB2 therapies.

  Original research paper Nature Reviews Cancer 7 158-159 doi:10.1038/nrc2100

• Immune regulation: Vitamin D3 promotes immune function in the skin

  

  The importance of vitamins for optimal health has been known for a long time, but two recent papers reveal a previously unknown role for vitamin D₃ in regulating immune responses in the skin.

  Original research paper Nature Reviews Immunology 7 174-175 doi:10.1038/nri2047

• Signalling: Building bridges with NF-κB

  

  The identification of a fourth inhibitor of nuclear factor-B (IB) protein by Alexander Hoffmann and colleagues has bridged the gap between the canonical and non-canonical nuclear factor-B (NF-B) signalling pathways. This signalling crosstalk describes the molecular mechanism for previously proposed links between inflammatory and developmental stimuli in the immune system.

  Original research paper Nature Reviews Immunology 7 175 doi:10.1038/nri2042

• P53: A signalling integration node

  

  Little is known about the mechanisms by which cells coordinate the many spatial and temporal signals they receive during development and tissue homeostasis. Stefano Piccolo and colleagues now show that the tumour-suppressor protein p53 links receptor Tyr kinase (RTK)-Ras-mitogen-activated protein kinase (MAPK) signalling and transforming growth factor- (TGF)-mediated transcriptional activity to drive mesoderm differentiation in Xenopus laevis embryos and to arrest growth in adult mammalian cells.

  Original research paper Nature Reviews Molecular Cell Biology 8 180 doi:10.1038/nrm2133

• Gene regulation: Transcription and translation get together

  

  Eukaryotes have evolved sophisticated mechanisms to fine tune gene and protein expression, but this complexity can come with a cost: the more regulatory steps involved the less rapid will be the response to any environmental cue. Robert Tjian and colleagues now show that, in Drosophila melanogaster, transcription and translation can be coupled, by using internal ribosome entry sites (IRESs), to guarantee a rapid response to a lack of nutrients.

  Original research paper Nature Reviews Genetics 8 168 doi:10.1038/nrg2069

• Neural circuit assembly: A molecular matchmaker

  

  Sensory processing relies on the formation of specific synapses between sensory neurons and projection neurons that carry coded information to the cortex. The development of these connections involves multiple mechanisms that are not fully understood. Three new papers demonstrate a role for the axon guidance molecule semaphorin 1A (SEMA1A) in axon and dendrite targeting in the olfactory system.

  Original research paper Nature Reviews Neuroscience 8 163 doi:10.1038/nrn2103

• Neurodegenerative disorders: Pathways to treatment

  

  The motor deficits observed in Parkinson's disease (PD) result from abnormalities in basal ganglia activity. An imbalance between the activity of striatal projection neurons targeting the substantia nigra pars reticulata (direct pathway) and those targeting the lateral globus pallidus (indirect pathway) is thought to be important in causing these deficits. A new study by Kreitzer and Malenka adds to our understanding of the molecular and electrophysiological differences between these pathways.

  Original research paper Nature Reviews Neuroscience 8 166 doi:10.1038/nrn2107

• Systems biology:Trapped in interaction

  

  Mechanical trapping of protein-DNA complexes allows systems-level measurement of intermolecular binding affinities.

  Original research paper Nature Reviews Neuroscience 4 202-203 doi:10.1038/nmeth0307-202b