Cell cycle

PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints. Lu, X., Nannenga, B. & Donehower, L. A. Genes Dev. 3 May 2005 (10.1101/gad.1291305)

The ataxia-telangiectasia mutated (ATM) and ataxia-telangiectasia and Rad-3 related (ATR) kinases phosphorylate various targets, including p53 and Chk1, following DNA damage. Lu et al. reported that the serine/threonine phosphatase PPM1D/Wip1, which is induced by p53, dephosphorylates Chk1 and p53. Overexpression of PPM1D inhibited both S-phase- and G2–M-damage-induced checkpoints, so PPM1D might restore cell-cycle homeostasis after completion of DNA repair.

Signalling

JNK extends life span and limits growth by antagonizing cellular and organism-wide responses to insulin signalling. Wang, M., Bohmann, D. & Jasper, H. Cell 121, 115–125 (2005)

In Drosophila melanogaster, calorie restriction extends lifespan by relieving the inactivation by insulin/insulin-like growth factor signalling (IIS) of Foxo to allow Foxo target-gene activation. Foxo also translocates to the nucleus in response to oxidative stress. The authors showed that Jun N-terminal kinase (JNK) signalling, which in D. melanogaster confers tolerance to oxidative stress and extends lifespan, induces Foxo nuclear localization and Foxo-dependent stress-response genes by antagonizing IIS. JNK also downregulates the production of D. melanogaster insulin-like peptide-2, thereby inhibiting IIS.

Morphogens

Lipoprotein particles are required for Hedgehog and Wingless signalling. Panáková, D. et al. Nature 435, 58–65 (2005)

How do lipid-anchored Wingless/Wnt and Hedgehog (Hh) induce long-distance target-gene expression? Panáková et al. showed that Wingless and Hh, as well as glycosylphosphatidylinositol (GPI)-linked proteins, associate and colocalize with the lipoprotein lipophorin, which is needed for lipid transport and long-range Hh and Wingless function. Lipid-linked morphogens and GPI-linked proteins are therefore moved (rather than simply released) by binding to lipoprotein particles.

Development

FGF signal interpretation is directed by Sprouty and Spred proteins during mesoderm formation. Sivak, J. M., Petersen, L. F. & Amaya, E. Dev. Cell 8, 689–701 (2005)

These authors identified two Sprouty and two Spred genes in Xenopus laevis, and showed that, in the early embryo, they inhibit distinct pathways mediated by fibroblast growth factor. The Sprouty proteins inhibit the activation of protein kinase Cδ, Ca2+ signalling and morphogenesis, whereas the Spreds inhibit the activity of mitogen-activated protein kinase and mesoderm specification. Their differential expression provides a putative mechanism to coordinate mesoderm formation and cell movements.