Apoptosis

P53AIP1, a potent mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53. Oda, K. et al. Cell 102, 849?862 (2000) [ PubMed]

The star of this story ? p53AIP1 ? is a newly cloned gene, the protein product of which localizes to the mitochondria. It causes apoptotic cell death by dissipating the mitochondrial transmembrane potential, and it could help to mediate p53-dependent apoptosis. After severe DNA damage, phosphorylation of a specific residue (serine 46) on p53 leads to apoptosis. The authors show that substitution of Ser 46 not only inhibits p53-dependent apoptosis, but also blocks expression of p53AIP1.

Translocation

Two intermembrane space TIM complexes interact with different domains of Tim23p during its import into mitochondria. Davis, A. J. et al. J. Cell Biol. 150, 1271?1282 (2000) [ PubMed]

How are mitochondrial proteins targeted for either insertion into the mitochondrial inner membrane or translocation into the matrix? Davis et al. show that the inner membrane protein Tim23p interacts with both known intermembrane space TIM complexes before reaching the Tim22p inner membrane translocon. But only its interaction with one of these complexes ? Tim9p?Tim10p ? is essential for correct targeting, leaving the mystery of what the Tim8p?Tim13p complex does intact.

Stem cells

Effects of eight growth factors on the differentiation of cells derived from human embryonic stem cells. Schuldiner, M. et al. Proc. Natl Acad. Sci. USA 97, 11307?11312 (2000) [ PubMed]

Until now there has been no systematic attempt to determine how growth factors affect the lineage choice of embryonic stem cells. This broad study correlates different growth-factor treatments with cell morphology and expression of markers for 11 tissues, derived from all three germ layers. It shows that what you put in biases, but doesn't absolutely determine, what you get out, and has obvious implications for stem-cell therapy.

Technology

Harnessing the ubiquitination machinery to target the degradation of specific cellular proteins. Zhou, P. et al. Mol. Cell 6, 751?756 (2000) [Contents page]

This paper uses a neat trick to functionally 'knock out' stable proteins ? by targeting them for proteasomal degradation. By engineering specific protein?protein interaction domains into one component of the stem cell factor complex, a multimeric ubiquitin-conjugating machine, Zhou and colleagues can send proteins to their death in both yeast and mammalian cells, and can measure the phenotypic consequences.