Research Highlights

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

April 2007

• Genomics: Beyond the usual suspects

  

  Profiling cancer mutations aims at providing a molecular portrait of each individual tumour sample to aid clinicians in improving diagnosis and tailoring the best therapy to each patient. However, the road to the clinic is not free from hurdles because of the cost and complexity of identifying the mutations that contribute to each cancer. Two recent studies have made important steps towards resolving these problems.

  Original research paper Nature Reviews Cancer 7 225 doi:10.1038/nrc2117

• Signalling: DNA damage is stressful

  

  DNA damage activates a complex signalling network that functions to mediate DNA repair and activate cell-cycle checkpoints. Michael Yaffe and colleagues now show that p53-deficient tumour cells rely on an alternative, parallel signalling pathway to activate cell-cycle checkpoints after treatment with DNA-damaging anticancer drugs.

  Original research paper Nature Reviews Cancer 7 226-227 doi:10.1038/nrc2116

• Tumorigenesis: Alternative view

  

  The splicing of human genes increases the variety of mRNAs and therefore proteins that one gene can encode. Adrian Krainer and colleagues show that, like deregulated transcription and translation, deregulated splicing can lead to tumour formation.

  Original research paper Nature Reviews Cancer 7 228 doi:10.1038/nrc2119

• Mechanisms of disease: Inhibiting γ-secretase activity

  

  The γ-secretase complex cleaves amyloid precursor protein (APP; resulting in the release of amyloid-β, a peptide that possibly causes Alzheimer's disease), Notch and other transmembrane proteins. Now, Spasic and colleagues identify retrieval to endoplasmic reticulum-1 (RER1) as an ectopic inhibitor of γ-secretase-complex assembly. This insight might open up new avenues for drug development.

  Original research paper Nature Reviews Molecular Cell Biology 8 272-273 doi:10.1038/nrm2156

• Heart disease: Unmasking molecular mechanisms

  

  Despite advances in the therapy of heart failure — such as beta blockers and renin–angiotensin antagonists — there is still a need for better therapies for many patients with this condition. Two recent papers have uncovered some of the molecular mechanisms involved in this disease, which could aid in the search for new therapeutic targets.

  Original research paper Nature Reviews Drug Discovery 6 271 doi:10.1038/nrd2298

• Synaptic plasticity: Balancing LTP and LTD

  

  Two major forms of synaptic plasticity, long-term potentiation (LTP) and long-term depression (LTD) are cellular processes involved in learning and memory. Although they produce opposite effects on synaptic excitability, both LTP and LTD can occur at the same synapse in response to different patterns of activation of NMDA (N-methyl-D-aspartate) receptors. This raises the question of whether specific mechanisms exist to prevent unwanted interference between the two processes. Collingridge and colleagues have now shown that LTP temporarily inhibits subsequent LTD induction at the same synapse and have uncovered a key role for glycogen synthase kinase 3β (GSK3β) in regulating the synaptic response downstream of NMDA receptor activation.

  Original research paper Nature Reviews Neuroscience 8 249 doi:10.1038/nrn2123

• The sensitive side of protein-DNA interactions

  

  Two groups describe unique methods to sensitively and quantitatively investigate protein-DNA interactions in vitro.

  Original research paper Nature Methods 4 298-299 doi:10.1038/nmeth0407-298b