These short, accessible highlights summarize and contextualize must-read papers related to cell signaling. These articles add background and context to summaries of primary research. 'In brief' articles emphasize key aspects of selected articles.
 | Angiogenesis: PI3K subunits branch out
The catalytic subunits of class IA phosphoinositide 3-kinases (PI3K) are activated by distinct signals and have discrete roles in angiogenesis and vascular remodeling.
Original research paper: Nature 453, 662-666 (2008) |
 | Colon cancer: Analyzing Ras specificity
Active N-Ras and K-Ras have different effects in colon cancer: K-Ras promotes proliferation and suppresses differentiation, whereas N-Ras protects cells from chemically induced apoptosis.
Original research paper: Nature Genetics 40, 600-608 (2008) |
 | Calcium signaling: Compounded aggregation
A screen for compounds that regulate autophagy has identified a cyclical inhibitory pathway in which cyclic AMP (cAMP) signaling increases intracellular calcium levels and stimulates calpain-mediated activation of Gαs, which raises cAMP levels.
Original research paper: Nature Chemical Biology 4, 295-305 (2008) |
 | NF-κB in hypoxia: And now for something completely different
The transcription factor NF-κB induces the expression of HIF-1α, providing a link between innate immunity and the hypoxic response.
Original research paper: Nature 453, 807-811 (2008) |
 | Oncogenic transformation: Invasion of the microvesicles
Glioma cells that express the oncogenic receptor EGFRvIII form microvesicles that fuse with neighboring, non-transformed cells to promote their oncogenic transformation.
Original research paper: Nature Cell Biology 10, 619-624 (2008) |
 | Mechanisms of disease: Stress and disease connect at mTORC1
Loss of tuberous sclerosis complex (Tsc) genes causes constitutive activation of mTOR, leading to endoplasmic reticulum (ER) stress and dysregulation of insulin receptor signaling.
Original research paper: Mol. Cell 29, 541-551 (2008) |
 | Antigen presentation: Prime time: insights into cross-presentation
Cross-presentation — the display of peptides derived from exogenous antigens on MHC class I molecules — is differentially regulated in dendritic cells by activation of discrete Toll-like receptor (TLR) pathways.
Original research paper: Nature Immunol. 9, 558-566 (2008) |
 | In brief: May 2008
Gene expression | Ageing | MHC molecules | B-cell signalling | Antiviral immunity | RNA world | Reward | Addiction | Cannabinoids | Traditional Chinese medicine | Cancer | Gene regulation | Malaria |
 | Signalling: An oncogene becomes RESTless
The abundance of the protein REST (repressor-element-1 silencing transcription factor) is regulated by a cell cycle-dependent ubiquitin pathway.
Original research paper: Nature 452, 365-369 (2008) |
 | Cell fate: The path to neurogenesis
In mice, oxidative conditions increase the interaction between the histone deacetylase Sirt1 and the transcription factor Hes1, which represses expression of the pro-neuronal-fate transcription factor Mash1 and promotes differentiation of neural progenitor cells.
Original research paper: Nature Cell Biol. 10, 385-394 (2008) |
 | Cardiovascular disease: Spice might protect the heart
Curcumin, the compound responsible for the yellow color of the curry spice turmeric, blocks cardiac hypertrophy by inhibiting p300-histone acetyltransferase (p300-HAT) activity, indicating a novel potential strategy for the prevention of heart failure.
Original research paper: J. Clin. Invest. 118, 879-893 (2008) |
 | NKT cells: NKT cells join the IL-17 gang
Natural killer T (NKT) cells can produce the immunomodulatory cytokine interleukin-17 (IL-17) following T-cell receptor ligation.
Original research paper: J. Immunol. 180, 5167-5171 (2008) |
 | T cells: Tuning T cells through the aryl hydrocarbon receptor
The aryl hydrocarbon receptor (AHR) transcription factor is an important ligand-dependent regulator of interleukin-17 (IL-17)-producing CD4+ T helper cells (TH17) and regulatory T (TReg) cell populations.
Original research paper: Nature 453, 65-71 (2008) |
 | Tumorigenesis: Ready and waiting
MYC is required for the interaction between the E2F1 transcription factor and its target gene promoters, which promotes activation of the E2F network and leads to cell proliferation.
Original research paper: Oncogene published online 17 March 2008 |
 | Microglia: Giving out dangerous signals
The release of heat-shock protein HSP60 from injured neurons activates Toll-like receptor 4 (TLR4) signaling, which stimulates microglia and facilitates neurodegeneration.
Original research paper: J. Neurosci. 27, 2320-2331 (2008) |
 | Gene regulation: Follow the ubiquitin
When used in chromatin immunoprecipitation (ChIP) experiments, an antibody to monoubiquitinated histone H2B (ubH2B) can map ubiquitination patterns across the genome or follow the modification of individual genes.
Original research paper: Nat. Cell Biol. 10, 483-488 (2008) |
 | Membrane trafficking: A maturing influence
A fluorescence resonance energy transfer (FRET) probe shows that Rab5 and its activator Gapex5 have key roles in phagosome maturation, potentially by mediating the fusion between phagosomes and early endosomes.
Original research paper: Nature 453, 241-245 (2008) |
 | Inflammation: Stopping before the damage is done
Overexpression of CUE-domain-containing protein 2 (CUEDC2) inhibits the phosphorylation of IKKα and IKKβ in response to tumor-necrosis factor signaling, thereby preventing the nuclear translocation of NF-κB.
Original research paper: Nature Immunol. 9, 533-541 (2008) |
 | Tumour suppressors: Motoring on down
Kinesin family member 1B (KIF1B) induces apoptosis in neurons in response to nerve growth factor withdrawal and is deleted in many different types of neuronal tumors.
Original research paper: Genes Dev. 22, 884-893 (2008) |
 | Neuroprotection: Staying active = staying alive
Activation of NMDA receptors in synapses, but not at extra-synaptic sites, has neuroprotective effects through stimulation of the antioxidant thioredoxin–peroxiredoxin enzyme system.
Original research paper: Nature Neurosci. 11, 476-487 (2008) |
 | Antiparasitics: Fighting back against resistant worms
Amino–acetonitrile derivatives are a new class of drugs that work by targeting nicotinic acetylcholine receptor subunits (nAChRs), and show promise for treating parasitic nematode infection in livestock.
Original research paper: Nature 452, 176-180 (2008) |
 | Membrane trafficking: Polar express
The vesicular coat protein clathrin is not only essential for endocytosis and cell signaling processes at the plasma membrane, it also has a role in intracellular trafficking and the maintenance of epithelial polarity.
Original research paper: Nature 452, 719-723 (2008) |
 | Mast cells: Food allergy unplugged
Interleukin-9 (IL-9) overexpression predisposes mice to oral antigen hypersensitivity by acting as a potent inducer of mastocytosis, which in turn increases intestinal permeability.
Original research paper: J. Exp. Med. 205, 897-913 (2008) |
 | Metastasis: Bringing up the rear
Blocking the function of the tetraspanin CD151 in vivo prevents tumor dissemination by inhibiting migration and access to the vasculature (intravasation) at primary tumor sites.
Original research paper: Cancer Cell 13, 221-234 (2008) |
 | Molecular neuroscience: Stress hormones Trk neurons into survival
The neuroprotective effects of glucocorticoids are mediated by the activation of the neurotrophin receptor TrkB in rats.
Original research paper: Proc. Natl Acad. Sci. USA 105, 4862-4867 (2008) |
 | Anticancer drugs: Scaffold to selectivity
Oncogenic mutations in the BRAF gene (such as V600E) correlate with increased severity and decreased response to chemotherapy in several human tumors; however, a new selective B-RafV600E kinase inhibitor has shown potent antimelanoma activity.
Original research paper: Proc. Natl Acad. Sci. USA 105, 3041-3046 (2008) |
 | Host response: Innate mimicry
A new class of virulence factors have been identified that are used by bacterial pathogens to interfere with Toll-like receptor (TLR) signaling.
Original research paper: Nature Med. 14, 399-406 (2008) |
 | Cell migration: Group voyage
Collective cell migration — the movement of cells in clusters, strands, sheets and tubes — is regulated by an evolutionarily conserved cascade that involves the Jun N-terminal kinase (JNK) signaling pathway.
Original research paper: Curr. Biol. 18, 532-537 (2008) |
 | Tumour immunology: Tumour surveillance by NKG2D
The expression of natural-killer group 2, member D (NKG2D) stimulatory receptor ligands is known to render tumor cells susceptible to NK-cell killing, and NKG2D has now been found to have an important role in tumor surveillance in spontaneous cancer models in vivo.
Original research paper: Immunity 28, 571-580 (2008) |
 | Therapy: Bad to the bone
Suppressing the hedgehog signaling pathway in cancers has potential therapeutic value; however, suppressing this pathway in young mice results in permanent and detrimental skeletal changes.
Original research paper: Cancer Cell 13, 249-260 (2008) |
 | Synaptic plasticity: A depressing TRP
The ion channel TRPV1 (transient receptor potential) induces a particular form of synaptic plasticity — long-term depression (LTD) — in the hippocampus.
Original research paper: Neuron 57, 746-759 (2008) |
 | Epigenetics: Pioneering the path from methylation to transcription
Epigenetic markers are interpreted by FOXA1 transcription factors, which bind to the methylated enhancers and open the chromatin in order to facilitate access by other transcription factors.
Original research paper: Cell 132, 958-970 (2008) |
 | Gene transfer: Knockouts with a touch of a zinc finger
Capitalizing on the imperfection of error-prone DNA repair, researchers generated knockout mammalian cell lines by targeting a nuclease to a gene of interest via a zinc-finger DNA-binding domain.
Original research paper: Proc. Natl. Acad. Sci. USA 105, 5809-5814 (2008) |
