Cell cycle

Targeted disruption of the three Rb-related genes leads to loss of G1 control and immortalization. Sage, J. et al. Genes Dev. 14 , 3037–3050 (2000) [PubMed]

Retinoblastoma and its close relatives p130 and p107 have overlapping functions in controlling the cell cycle. To investigate the functions of each protein in vivo, the authors generated single, double and triple-knockout mouse embryonic fibroblasts. The triple knockouts have a shortened cell cycle, show characteristics of transformed cells, and do not undergo G1 arrest in response to several factors. These results, say the authors, “further the link between loss of cell cycle control and tumorigenesis”.

Development

DNA methylation in Drosophila melanogaster. Lyko, F., Ramsahoyer, B. H. & Jaenisch, R. Nature 408 , 538–539 (2000) [PubMed]

Inactive regions of many eukaryotic genomes contain methylated cytosine residues, but the fruitfly was thought to be an exception until recently. Jaenisch and colleagues now reveal that this methylation is restricted to the early stages of embryonic development. The authors show that methylation decreases during later stages of development, and they predict that this could be due to reduced expression of the enzyme responsible, DNA methyltransferase.

Prions

Binding of disease-associated prion protein to plasminogen. Fischer, M. B. et al. Nature 408 , 479–483 (2000) [PubMed]

PrPSc is associated with transmissible spongiform encephalopathies, but deposition of this protein alone is not sufficient to damage the brain, indicating that it interacts with other cellular factors to cause disease. Fischer et al. now show that blood plasminogen binds to PrPSc but not to normal PrPC. Plasminogen is therefore the first molecule that can reliably discriminate between normal and pathological prion proteins, making it a useful tool for diagnostic purposes.

Cell signalling

InsP4 facilitates store-operated calcium influx by inhibition of InsP3 5-phosphatase. Hermosura, M. C. et al. Nature 408 , 735–740 (2000) [PubMed]

Is inositol-1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4), like inositol-1,4,5-trisphosphate (Ins(1,4,5)P3) a calcium-releasing second messenger. This study reveals that low Ins(1,3,4,5)P4 concentrations collaborate with Ins(1,4,5)P3 by inhibiting the enzyme that inactivates Ins(1,4,5)P3, whereas higher concentrations have the opposite effect by blocking the Ins(1,4,5)P3 receptor. By sacrificing a proportion of the Ins(1,4,5)P3 pool to make Ins(1,3,4,5)P4, cells can turn calcium signals up or down, according to their needs.