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Increasing the activity of the p53 tumour suppressor in mice protects them from cancer, but this has also been associated with an unwanted side effect, specifically, premature ageing. However, a new strain of 'super p53' mice are resistant to cancer but age gracefully, suggesting that protection from cancer doesn't always come at a price.
The p53-binding protein 53BP1 has been implicated in DNA damage responses. Three new reports indicate that 53BP1 is central to both the S and G2 checkpoints after exposure to ionizing radiation (IR). 53BP1 participates in the organization of nuclear foci and facilitates the phosphorylation of specific substrates by the checkpoint kinase, ataxia-telangiectasia mutated (ATM).
Asymmetric cell divisions are pivotal throughout development and generate cell diversification within the embryo. The formation of polar bodies during oocyte meiotic maturation provides the most extreme case of size difference between two daughter cells. New work in this issue indicates that formin-2, a microfilament-binding protein, is required for the eccentric positioning of the meiotic spindle that determines these unequal divisions.
The pivotal role of phospholipase C (PLC) in calcium signalling is well established. A product of PLC, inositol 1,4,5-trisphosphate (InsP3), is an important and almost ubiquitous signal for the release of calcium from intracellular endoplasmic reticulum stores. Recent work has demonstrated that the PLC-γ isoform is essential for activating calcium entry into cells through channels in the plasma membrane.
The organization of signalling complexes represents the coalescence of cell biology and signal transduction. Recent work on Dishevelled (Dvl), a multifunctional component of the Wnt–Frizzled (Fz) signalling pathway, ascribes vesicle- and actin-binding properties to a single domain within the protein. This could represent a critical point for divergence of the Wnt signalling pathway.
Neuregulin (NRG) is a crucial regulator of oligodendrocyte development, strongly promoting both the proliferation of oligodendrocyte precursor cells and the survival and maturation of oligodendrocytes. How can the same growth factor mediate such different effects? New work in this issue of Nature Cell Biology implicates an integrin-mediated switch in signalling that results in the loss of the proliferative response and the enhancement of survival and maturation.
The Chk2 checkpoint kinase is implicated in radiation-induced apoptosis. New findings suggest that radiation induces dissociation of Chk2 from the promyelocytic leukemia gene product (PML). Thus, PML nuclear bodies may function as regulated storage depots, releasing specific proteins in response to specific types of cellular stress.
The combined use of laser ablation and live imaging in Drosophila melanogaster embryos provides new ways to visualize the dynamics of wound healing. Analysis of lesions made in living embryos mutant for small GTPases reveal distinct and unexpected roles for actin cables and protrusions in wound repair. Hole closure is definitely more complex than simply pulling a string.
The budding of a cargo-laden clathrin-coated pit (CP) from the plasma membrane (PM) during receptor-mediated endocytosis is a paradigm of vesicular transport. A recent study published in Nature Cell Biology helps us visualize the creation of the clathrin-coated vesicle, and the involvement of dynamin and actin as potential 'midwives' in the process. Still, it remains a matter of faith as to exactly when life begins for the coated vesicle.
The Golgi apparatus, in common with other cytoplasmic organelles, must be replicated during the cell cycle. Recent studies using green fluorescent protein (GFP) fusions, suggest that this process may occur by different mechanisms in different organisms. In this issue of Nature Cell Biology, striking new data shows an apparent de novo formation of the Golgi in the daughter cells of budding yeast.
The events of mitosis must occur in a precise sequence and in rapid succession to achieve proper chromosome segregation. At each key stage, mitotic checkpoints monitor whether everything is as it should be before proceeding, ensuring orderly progression through mitosis. Now, a new checkpoint has been identified that blocks anaphase onset in response to misoriented mitotic spindles.
The molecular pathways involved in wiring the brain have just begun to be elucidated. Work in this issue of Nature Cell Biology has uncovered inhibitory interactions between two such pathways: Roundabout (Robo) and N-Cadherin. This discovery provides a potential mechanistic understanding of how pathways are used in a coordinated manner to guide axons.
The insulin- and growth factor-stimulated protein kinases protein kinase B (PKB)/Akt and p70 S6 ribosomal kinase (S6K) are crucial regulators of cell growth. Recent advances, supported by work in this issue of Nature Cell Biology, have indicated that the tumour suppressor tuberous sclerosis complex-2 (TSC2) functions as an antagonist of S6K activation, an inhibition that is relieved by PKB-mediated phosphorylation of TSC2. In contrast to some previous models, these findings indicate that PKB functions upstream of S6K.
Some thirty years ago, a model was proposed to explain patterning of the vertebrate limb along its proximal–distal axis. This model was based on the ability of cells to measure time to assess their position. Two recent publications in Nature present data that may be difficult to reconcile with the early model. One report proposes that the limb is already specified in minute form in the early limb bud, whereas the other focuses on fibroblast growth factor (FGF) signalling from the apical ridge.
