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.
 | Pathogen response: NLRX1 is a prospective, selective anti-infective
The NLRX1 receptor inhibits the production of antiviral type I interferon β (IFN-β) by blocking the interaction between the RNA helicase RIG-I and the mitochondrial antiviral signaling protein MAVS.
Original research paper: Nature 451, 573-577 (2008) |
 | Cell cycle: GABA keeps embryonic stem cells in check
γ-aminobutyric acid (GABA) receptor-mediated signaling causes S-phase cell cycle arrest in embryonic stem (ES) cells and neural crest stem (NCS) cells by promoting phosphorylation of histone H2AX.
Original research paper: Nature 451, 460-464 (2008) |
 | EGF signaling: The GEP100 pathway to invasion
When stimulated by epidermal growth factor (EGF), the guanine nucleotide-exchange factor GEP100 interacts with the EGF receptor (EGFR) to specifically activate the Arf6 GTPase and induce breast cancer cell invasion.
Original research paper: Nat. Cell Biol. 10, 85-92 (2008) |
 | Bone morphogenetic protein antagonists: Mighty morphin small molecules
A screen for chemical antagonists of the bone morphogenetic protein (BMP) pathway has identified dorsomorphin as a selective inhibitor of BMP receptor-mediated SMAD1/5/8 phosphorylation.
Original research paper: Nature Chemical Biology 4, 33-41 (2008) |
 | HIV: The escape artist
A common mutation in an HIV viral peptide not only impedes its recognition by cytotoxic T lymphocytes but also facilitates its binding to ILT (immunoglobulin-like transcript) receptors, impairing the maturation and response of immune cells.
Original research paper: J. Exp. Med. 204, 2813-2824 (2007) |
 | Lung inflammation: Disarming neutrophils in cystic fibrosis
The antibacterial function of neutrophils is disabled in the lungs by the cleavage of CXC-chemokine receptor 1 (CXCR1) in patients with cystic fibrosis.
Original research paper: Nature Med. 13, 1423-1430 (2007) |
 | In brief: January 2008
Circadian rhythms | T-cell development | Targeted therapeutics | Genomics | Axon growth | Glucose homeostasis | G-protein-coupled receptors | Imaging and visualization |
 | Tumour suppressors: Crystal clear
Elucidating the crystal structure of the retinoblastoma amino-terminal domain (RBN) has provided insight into the way it contributes to RB function and tumor suppression.
Original research paper: Mol. Cell 28, 371-385 (2007) |
 | Neurodegenerative disorders: Normalizing Parkinsonian networks
A therapy for Parkinson's disease involving gene delivery directly to the subthalamic nucleus (STN) normalized metabolic changes occurring in brain areas associated with motor activity but not in areas involved in cognition.
Original research paper: Proc. Natl Acad. Sci. USA 104, 19559-19564 (2007) |
 | Diabetes: Concentrating the benefits of red wine?
Researchers have identified a series of small-molecule activators for the protein deacetylase SIRT1 that show promising beneficial effects in animal models of type 2 diabetes.
Original research paper: Nature 450, 712-716 (2007) |
 | Bacterial virulence: The cycle of success for Legionella
Two papers have provided an insight into the mechanisms that Legionella pneumophila uses to subvert the host-cell vesicular trafficking pathway to create its replicative niche.
Original research paper: Science 318, 974-977 (2007) |
 | Stem cells: Ringing the changes
In embryonic stem cells, RING1-mediated ubiquitination of histone H2A restricts RNA polymerase II from transcribing genes that would otherwise promote development and differentiation.
Original research paper: Nature Cell Biol. 9, 1428-1435 (2007) |
 | Inflammation: TIM3: dual role in immunity
In addition to its known role as a negative regulator of T helper 1 (TH1)-cell responses, TIM3 (T-cell immunoglobulin domain and mucin domain 3) can promote pro-inflammatory responses by affecting the production of tumor-necrosis factor (TNF) and inducing the expression of nuclear factor-κB (NF-κB) in dendtiric cells.
Original research paper: Science 318, 1141-1143 (2007) |
 | Tumorigenesis: Keeping a good thing down
Myc-induced tumorigenesis causes widespread repression of microRNAs, suggesting that re-expression of microRNAs could block the growth of Myc-positive tumors.
Original research paper: Nature Genet. 40, 43-50 (2008) |
 | Neurotransmission: Getting vesicles ready for action
CAPS (Ca2+-dependent activator protein of secretion) proteins play an important role in priming synaptic vesicles for exocytosis and neurotransmitter release.
Original research paper: Cell 131, 796-808 (2007) |
 | Metabolic disease: New opportunity for serotonin receptor agonists
Serotonin 2C receptor agonists have been shown to improve glucose tolerance and reduce plasma insulin levels, indicating that pharmacological modulation of serotonin receptor activity may be an effective new approach to treat type 2 diabetes.
Original research paper: Cell Metab. 6, 398-405 (2007) |
 | Chemical biology: Smaller can be better
Researchers have split the FlAsH–ReAsH tetracysteine recognition sequence into two pieces to show that these small-molecule fluorophores can report protein folding or protein–protein interactions.
Original research paper: Nat. Chem. Biol. 3, 779-784 (2007) |
 | DNA damage: Conducting repair
Ubiquitination of chromatin surrounding a double-stranded DNA break facilitates the recruitment of proteins that mediate the DNA damage response, adding another level of complexity to the regulation of DNA repair.
Original research paper: Cell 131, 901-914 (2007) |
 | Signalling: The ins and outs of Ca2+ signalling in mast cells
The ER Ca2+ sensor STIM1 (stromal interaction molecule 1) and the calcium-release-activated calcium (CRAC) channel component CRACM1 are required for mast-cell function, revealing a key role for store-operated Ca2+ influx in mediating allergic reactions.
Original research paper: Nature Immunol. 9, 81-88 (2007) |
 | Tumour suppressors: Keeping Trim
Tripartate motif-containing 24 (Trim24) appears to restrict the genesis of hepatocellular carcinoma (HCC) by inhibiting the retinoic acid (RA) transcriptional network.
Original research paper: Nature Genet. 39, 1500-1506 (2007) |
 | Ageing: The ups and downs of ageing
Expression-profiling studies of ageing have benefited from the free AGEMAP gene expression database that catalogues ageing-related gene expression changes for 16 tissues from a single mouse strain using a standardized methodology.
Original research paper: PLoS Genet. 3, e201 (2007) |
 | Neurodegenerative disorders: ASIC mind
Acid-sensitive ion channel 1 (ASIC1) is a neuronally expressed, proton-gated cation channel that might contribute to the pathophysiology of multiple sclerosis (MS), suggesting that compounds that block the channel might be valuable therapeutics for slowing the progression of this disease.
Original research paper: Nature Med. 13, 1483-1489 (2007) |
 | DNA replication: Wakey wakey!
The DNA-damage response (DDR) kinases ATR and CHK1 modulate the initiation of DNA replication by suppressing replication from secondary 'dormant' origin sites.
Original research paper: Genes Dev. 21, 3331-3341 (2007) |
 | Lymphocyte development: SLAM dunk for innate T cells
The SLAM (signaling lymphocytic activation molecule) family of receptors regulate the development of a specific subset of T cells with innate-like characteristics that arise from thymocyte selection.
Original research paper: Immunity 27, 751-762 (2007) |
 | Therapeutics: Smac it to them!
Compounds that activate or mimic the pro-apoptotic protein SMAC (second mitochondrial-derived activator of caspase) cause regression of human lung cancer xenografts by increasing apoptotic signaling through tumor necrosis factor receptor 1 (TNFR1).
Original research paper: Cell 131, 682-693 (2007) |
 | Developmental biology: Retinoic acid passes the morphogen test
The anterior-to-posterior retinoic acid (RA) concentration gradient is established by the opposing effects of a locally acting, RA-induced degradation enzyme and fibroblast growth factor (Fgf), which represses RA degradation.
Original research paper: PLoS Biol. 5, e304 (2007) |
 | Neurogenesis: Par for the course
Par (partitioning defective) proteins are well-established polarity markers, but they also have a crucial role in maintaining the proliferation potential of ventricular zone progenitor cells to regulate the size and thickness of the cortex.
Original research paper: Development 135, 11-22 (2008) |
 | G-protein-coupled receptors: Crystal clear
A collection of papers describing the crystal structure of the G-protein-coupled β2-adrenergic receptor (β2AR) may facilitate the development of drugs that specifically interfere with ligand-receptor binding of related GPCRs.
Original research paper: Science 318, 1258-1265 (2007) |
