Apoptosis

Histone H2B deacetylation at lysine 11 is required for yeast apoptosis induced by phosphorylation of H2B at serine 10. Ahn, S.-H. et al. Mol. Cell 24, 211–220 (2006)

Histone modifications are known to regulate a number of cellular processes. In growing yeast, the histone protein H2B is acetylated on Lys11, whereas phosphorylation of the adjacent Ser10 residue has been linked to the induction of apoptosis. Ahn et al. now show that hydrogen peroxide treatment of growing cells first causes Lys11 to be deacetylated, followed by the subsequent phosphorylation of Ser10 and apoptosis. The deacetylase enzyme Hos3 mediates the first step, whereas phosphorylation depends on the kinase Ste20. The authors propose that a concerted series of histone modifications control the switch from cell growth to cell death.

Development

Canonical notch signaling functions as a commitment switch in the epidermal lineage. Blanpain, C. et al. Genes Dev. 20, 3022–3035 (2006)

The formation of mammalian epidermis involves the differentiation and migration of basal-layer progenitor cells to suprabasal spinous cells. Blanpain and colleagues show that Notch signalling commits dividing progenitor cells to becoming spinous cells. Activated Notch intracellular domain (NICD) and its signalling partner RBP-J are both required to repress expression of progenitor-cell genes and to activate spinous-cell gene expression. Spinous-cell gene activation depends on the NICD–RBP-J target gene HES1, whereas progenitor-cell gene repression occurs through a HES1-independent mechanism.

Signal transduction

Global, in vivo , and site-specific phosphorylation dynamics in signaling networks. Olsen, J. V. et al. Cell 127, 635–648 (2006)

Protein phosphorylation functions as a reversible switch in many signalling cascades. Using a high-throughput mass-spectrometry-based technique, the authors detected 6,600 protein phosphorylation sites in HeLa cells and monitored changes in phosphorylation during epidermal growth factor stimulation. Phosphorylation is modulated by at least twofold at 14% of phosphorylation sites and proteins that contain multiple phosphorylation sites are often regulated independently.

Sumoylation

Regulation of MBD1-mediated transcriptional repression by SUMO and PIAS proteins. Lyst, M. J. et al. EMBO J. 26 Oct 2006 (doi: 10.1038/sj.emboj.7601404)

Methylated DNA can serve as a binding site for methyl-CpG-binding domain (MBD) proteins, which, in turn, recruit co-repressor complexes that modify chromatin into an inactive state. Lyst et al. found that the activity of MBD1 can be regulated by sumoylation near its C terminus by two PIAS-family members, PIAS1 and PIAS3. Sumoylated MBD1 still binds to methylated DNA, but neither recruits the histone methylase SETDB1 nor silences gene expression in HeLa cells. MBD1 is proposed to function as a scaffolding platform on methylated DNA that can be regulated through sumoylation.