Research Highlights

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

April 2008

• Metabolism: Warburg effect revisited

  

  It was Otto Warburg who first noted the difference between metabolism in cancer cells and that in normal adult tissues: cancer cells take up glucose at higher rates than normal tissue but use a smaller fraction of this glucose for oxidative phosphorylation. This effect is known as aerobic glycolysis or the Warburg effect. Lewis Cantley and colleagues now report that the human M2 (fetal) isoform of pyruvate kinase (PKM2), an enzyme that is involved in glycolysis, is a phosphotyrosine-binding protein and promotes the Warburg effect.

  Original research paper Nature Reviews Molecular Cell Biology 8 247 doi:10.1038/nrm2384

• DNA repair: A major Ku?

  

  Since its discovery, BCL2 has been viewed as a mild-mannered oncogene—tumorigenic over a protracted time course in comparison with seasoned professionals such as MYC and KRAS. However, over recent years evidence has been emerging that BCL2 might have a more sinister function: that it might be involved in inhibiting DNA repair.

  Original research paper Nature Reviews Cancer 8 248 - 249 doi:10.1038/nrc2360

• Tumorigenesis: Turning the hands of time

  

  Mammals exhibit oscillations in metabolism, physiology and behaviour with a near 24 h periodicity, a phenomenon known as the circadian rhythm. Changes to circadian oscillations, or phases, are associated with an increased risk of cancer and accelerated tumour progression, although why this might be remains unclear. The van der Horst laboratory now provide evidence for a link between DNA damage response (DDR) signalling and the scheduling of circadian rhythms.

  Original research paper Nature Reviews Cancer 8 250 - 251 doi:10.1038/nrc2363

• Innate immunity: TLR4 signalling

  

  Toll-like receptor 4 (TLR4) is unique among TLRs in its ability to activate two distinct signalling pathways — one pathway is activated by the adaptors TIRAP (Toll/interleukin-1-receptor (TIR)-domain-containing adaptor protein) and MyD88, which leads to the induction of pro-inflammatory cytokines, and the second pathway is activated by the adaptors TRIF (TIR-domain-containing adaptor protein inducing interferon-β ) and TRAM (TRIF-related adaptor molecule), which leads to the induction of type I interferons. Until now, it had been believed that these two signalling pathways were activated simultaneously at the plasma membrane. Now, a study from Ruslan Medzhitov's laboratory shows that the two signalling pathways are induced sequentially and that the TRAM-TRIF pathway is only operational from early endosomes following endocytosis of TLR4.

  Original research paper Nature Reviews Immunology 8 241 doi:10.1038/nri2301

• Nuclear transport: Signalling and transport converge

  

  Researchers have found an unexpected link between the Ras-extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3K) signalling pathways and the regulation of nucleocytoplasmic transport.

  Original research paper Nature Reviews Molecular Cell Biology 9 265 doi:10.1038/nrm2386