Research Highlights

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

May 2007

• Metastasis: Inflammatory invasion

  

  Inflammation has been proposed to promote metastasis, but how these two processes are linked is unknown. Michael Karin and colleagues have now shown a role for IB kinase (IKK), possibly activated by tumour-infiltrating inflammatory cells, in promoting prostate cancer metastasis independently of nuclear factor B (NFB).

  Original research paper Nature Reviews Cancer 7 319 doi:10.1038/nrc2135

• Tumorigenesis: Branching defects

  

  The Ras genes are some of the most frequently mutated genes in human cancer, but despite decades of study many aspects of Ras function — and dysfunction — have still to be fully elucidated. This is probably due to the complexity of the Ras signalling network, which is modulated in a context-dependent manner by various cross-talk and feedback mechanisms that have not yet been studied in detail. Now Alice Shaw, Tyler Jacks and colleagues show that a Ras–mitogen-activated protein kinase (MAPK) antagonist, Sprouty 2 (Spry2), regulates oncogenic Kras during development and tumorigenesis.

  Original research paper Nature Reviews Cancer 7 321 doi:10.1038/nrc2134

• Heads or tails? You lose!

  

  Mutations in the tumour suppressor p53 generally cause the loss of tumour-suppressor function. However, some p53 mutants have novel activities that promote oncogenesis. A new study in Nature Cell Biology sheds light on the mechanism that underlies such gain-of-function p53 mutants.

  Original research paper Nature Reviews Molecular Cell Biology 8 344 doi:10.1038/nrm2168

• Cell death: The clock is ticking

  

  Platelets, the small anuclear cytoplasmic fragments that function in blood clotting and wound healing, circulate in the blood stream for a limited period before being destroyed. New findings reported in Cell suggest that their lifespan is determined by the interplay between pro-survival and pro-apoptotic factors.

  Original research paper Nature Reviews Molecular Cell Biology 8 340 - 341 doi:10.1038/nrm2169

• Innate immunity: Triggering RIG-I

  

  When viral RNA enters the cytosol, a recently identified cytosolic receptor known as retinoic-acid-inducible gene I (RIG-I) is on hand to detect it and trigger a type I interferon (IFN)-mediated response that protects the host against viral infection. RIG-I is known to partner with MAVS (mitochondrial antiviral signalling protein; also known as VISA, IPS1 and CARDIF) to transmit its message to the nucleus. Reporting in Nature, Jae Jung and colleagues have identified another interacting partner for RIG-I that is crucial for the RIG-I-triggered response. They show that the E3 ubiquitin ligase TRIM25 (tripartite-motif-containing protein 25) binds and ubiquitylates RIG-I, and this enables MAVS to bind to RIG-I and induce downstream signalling.

  Original research paper Nature Reviews Immunology 7 321 doi:10.1038/nri2081

• Lymphocyte migration: Exiting lymphoid organs

  Sphingosine 1-phosphate (S1P) is an extracellular signalling molecule that acts through S1P receptor 1 (S1P1)–S1P5 to promote the egress of lymphocytes from lymphoid organs into the blood and lymph. But whether S1P promotes egress directly is not known, and nor is the source of S1P. Now, Pappu and colleagues show that different sources supply S1P to the blood and lymph, and that S1P acts directly on lymphocytes to induce their egress.

  Original research paper Nature Reviews Immunology 7 323 doi:10.1038/nri2074

• Circadian genetics: Setting the pace: three's company

  

  Circadian clocks regulate the daily rhythm of many biological processes. Timing is set through biochemical oscillators that sense and adjust to different environmental cues. A recent study now defines the molecular mechanisms of an oscillator that can comprise just three clock proteins and be reconstituted in a test tube.

  Original research paper Nature Reviews Genetics 8 326 - 327 doi:10.1038/nrg2115

• Protein-protein interactions: better by the dozen

  

  A combined reanalysis of the two largest yeast protein-protein interaction studies to date provides a large consolidated data set, with a level of accuracy matching the reliability of small-scale experiments.

  Original research paper Nature Methods 4 389 doi:10.1038/nmeth0507-389