Cancer

Antiapoptotic BCL-2 is required for maintenance of a model leukemia. Letai, A. et al. Cancer Cell 6, 241–249 (2004)

Resistance to apoptosis, often resulting from the overexpression of anti-apoptotic proteins, is common in cancers, but it remains uncertain whether defects in apoptosis are essential for tumour maintenance. Letai et al. investigated this idea using mice that develop leukaemia in which the overexpression of the key anti-apoptotic protein B-cell lymphoma-2 (BCL2) could be conditionally turned off. Eliminating BCL2 rapidly induces apoptosis and leukaemia remission, providing support for the potential of BCL2 as an anticancer drug target, and suggesting that if apoptotic defects are eliminated, inherent death signals would kill cancer cells.

Antibacterials

The nisin–lipid II complex reveals a pyrophosphate cage that provides a blueprint for novel antibiotics. Hsu, D. S. et al. Nature Struct. Mol. Biol. 11, 963–967 (2004)

The family of lanthionine-containing antibiotics, of which nisin is a member, could be promising candidates for alleviating the growing problem of antibiotic resistance. Nisin acts by binding to lipid II, an essential precursor of cell-wall synthesis. Hsu and colleagues report the solution structure of the complex of nisin and lipid II, which indicates possibilities for the structure-based design of novel antibiotics.

Chemical genetics

Identification of novel small-molecule inhibitors of severe acute respiratory syndrome-associated coronavirus by chemical genetics. Kao, R. Y. et al. Chem. Biol. 11, 1293–1299 (2004)

Kao et al. screened ∼50,000 structurally diverse compounds for their capacity to protect cells from the cytopathic effects induced by the severe acute respiratory syndrome-associated coronavirus (SARS-CoV). Of around 100 compounds that were found to have strong antiviral activity, several were further characterized and found to target specific proteins involved in viral pathogenesis; these compounds represent possible leads for drug development.

Diabetes

Possible novel therapy for diabetes with cell-permeable JNK-inhibitory peptide. Kaneto, H. et al. Nature Med. 10, 1128–1132 (2004)

The activity of c-Jun N-terminal kinase-1 (JNK1) is known to be abnormally elevated in several tissues in the diabetic state, and activation of the JNK1 pathway interferes with insulin action. Kaneto et al. treated diabetic mice with a cell-permeable JNK-inhibitory peptide derived from the JNK-binding domain of JNK-interacting protein-1, and found that it markedly improved insulin resistance and ameliorated glucose tolerance, indicating that the JNK pathway has a key role in diabetes.