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.
 | Inflammatory liver fibrosis: TLR4 takes its Toll on Bambi
The TLR4 pathway regulates TGF-β signaling to promote hepatic fibrosis in response to liver inflammation and injury.
Original research paper: Nature Medicine 13, 1324-1332 (2007) |
 | Nutrient deprivation: Cell splitting TORture
Nutrient deprivation activates the mitogen-activated protein kinase (MAPK) stress response pathway protein Sty1 via Tor (target of rapamycin) signaling.
Original research paper: Nature Cell Biology 9, 1263-1272 (2007) |
 | Phospholipid recognition: Saying BAI-BAI to apoptotic cells
Phosphatidylserine, which decorates apoptotic cells and triggers macrophage engulfment, is a novel ligand for the BAI1 and Tim4 transmembrane receptors and promotes corpse uptake by activating Rac.
Original research paper: Nature 450, 430-434 (2007) |
 | Hedgehog signaling: And SMO it was SAID
The smoothened auto-inhibitory domain (SAID) consists of a cluster of arginine residues and is responsible for translating graded hedgehog signals into distinct intracellular responses.
Original research paper: Nature 450, 252-258 (2007) |
 | Toll-like signaling: Increased RSKs produce higher Tolls
A non-canonical MAPK signaling pathway has been identified in mouse dendritic cells (DCs) in which the activity of the mitogen-activated protein kinases (MAPKs) p38 and Erk converges on the p90 ribosomal S6 kinases (RSKs).
Original research paper: Nat Immunol. 8, 1227-1235 (2007) |
 | Dendritic cells: Plasmacytoid dendritic cells in psoriasis
In autoimmune diseases such as psoriasis, the antimicrobial peptide LL37 can stimulate plasmacytoid dendritic cells through an interaction with 'self DNA', leading to interferon-mediated activation of autoimmune T cells.
Original research paper: Nature 449, 564–569 (2007) |
 | Ageing: Falling p53 function
As mice age, falling levels of ataxia-telangiectasia mutated (ATM) lead to a decline in p53 transcription, suggesting a possible explanation for the link between ageing and cancer.
Original research paper: Proc. Natl Acad. Sci. USA 104, 16633–16638 (2007) |
 | In brief: November 2007
Mechanotransduction | DNA repair | T-cell responses | Inflammation | Microenvironment | Inflammation | Angiogenesis | Chromatin | Glia | Computational Biology | Cancer | RNA interference | Gene regulation |
 | Genetic screens: Epistasis on the double
A quick method for generating double mutants in the fission yeast Schizosaccharomyces pombe will enable high-throughput epistasis analysis and allow the eventual construction of a genome-wide map of genetic interactions.
Original research paper: Nature Methods 4, 861–866 (2007) |
 | Systems neuroscience: No food in the CART
Serotonin receptor-mediated upregulation of the neuropeptide cocaine- and amphetamine-regulated transcript (CART) in the nucleus accumbens suppresses appetite during amphetamine-induced anorexia in mice.
Original research paper: Proc. Natl Acad. Sci. USA 104, 16335–16340 (2007) |
 | Protein biochemistry: Interaction in solution
Interferometry, which quantifies changes in the refractive index, can be used to measure interactions between unlabelled macromolcules in free solution.
Original research paper: Science 317, 1732–1736 (2007) |
 | Mechanisms of disease: Kinases out of control — brake line cut!
Pathogenic mutations in receptor tyrosine kinases (RTKs) cause various human cancers by disengaging a molecular brake that inhibits RTK activation.
Original research paper: Mol. Cell 27, 717–730 (2007) |
 | Immune regulation: A fourth dimension to the stromal scaffold
As well as providing a three-dimensional scaffold on which immune cells travel, fibroblastic reticular cells (FRCs) also produce the key T-cell survival factor interleukin-7 (IL-7) and are the targets of persistent viral infection.
Original research paper: Nature Immunol. 8, 1255–1265 (2007) |
 | Tumour suppressors: Sorting it out
The tumor suppressor EphB works by compartmentalizing colorectal cancer cells to restrict the spread of tumor cells into ephrin-B1-positive areas of the intestine.
Original research paper: Nature Genet. 39, 1376–1383 (2007) |
 | Development: Mutual collaboration
Hox proteins selectively activate or repress target genes in different tissues through 'collaboration' — co-regulation of a target gene without a direct interaction — with cofactors such as Smads.
Original research paper: Development 134, 3585–3592 (2007) |
 | Learning and memory: Remodel to reconsolidate
Inhibitor of κB kinase α (IKKα)-mediated regulation of chromatin remodeling and binding of nuclear factor-κB (NF-κB) to DNA both play an important role in memory reconsolidation in the contextual conditioned fear paradigm.
Original research paper: Neuron 55, 942–957 (2007) |
 | Inflammatory disorders: Chronically amplifying disease
Triggering receptor expressed on myeloid cells 1 (TREM1) has a pathogenic role in chronic inflammatory disorders and may be a therapeutic target for the treatment of inflammatory bowel disease.
Original research paper: J. Clin. Invest. 117, 3097–3106 (2007) |
 | Cell polarity: Persistently on PAR
The PAR (partitioning-defective) polarity complex and TIAM1 guanine nucleotide exchange factor regulate the polarized migration of free epithelial cells.
Original research paper: Curr. Biol. 17, 1623–1634 (2007) |
 | Inflammation: Cryopyrin — another guise of death
The cytoplasmic inflammasome complex component cryopyrin can cause necrosis-like cell death through an inflammatory response pathway that is independent of inflammasome formation.
Original research paper: Cell Host Microbe 2, 147–159 (2007) |
 | Autophagy: Tumour or death?
In addition to its known role in promoting apoptosis, the BAX interacting factor BIF1 can elicit autophagy-induced cell death through interactions with the autophagy-regulating proteins beclin 1 and UVRAG.
Original research paper: Nature Cell Biol. 9, 1142–1151 (2007) |
 | Molecular neurobiology: Chained together
Dynamin 3, homer 1 and shank provide a physical link between the endocytic zones and postsynaptic density in neurons, and regulate the endocytic cycling of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors.
Original research paper: Neuron 55, 874–889 (2007) |
 | Bone diseases: Central control
The neuropeptide neuromedin U (NMU) stimulates the NMU receptor subtype 2 to modulate leptin-dependent regulation of bone mass.
Original research paper: Nature Med. 13, 1234–1240 (2007) |
 | Gene expression: Basal crosstalk
A quantitative proteomic screen has revealed that the basal transcription factor TFIID preferentially binds to histone H3 that is trimethylated at lysine 4 (H3K4me3), providing a clear link between chromatin modification and transcriptional activity.
Original research paper: Cell 131, 58–69 (2007) |
 | B-cell development: (micro)Control of B-cell development
The microRNA miR-150 binds to c-Myb mRNA and inhibits protein expression, which blocks the pro- to pre-B-cell transition during B-cell development.
Original research paper: Cell 131, 146–159 (2007) |
 | Genetics: Networks uncover new cancer susceptibility suspect
A network built from genes with similar expression profiles to known breast cancer oncogenes has identified the hyaluronan-mediated motility receptor (HMMR) gene as a novel locus for breast cancer susceptibility.
Original research paper: Nature Genet. 39, 1338–1349 (2007) |
 | Anticancer drugs: Turning cancer off
Increased PI3K pathway signaling in tumors heightens eukaryotic translation initiation factor 4E (EIF4E) activity; application of EIF4E-specific antisense oligonucleotides shrinks tumors in mice with no overt side effects.
Original research paper: J. Clin. Invest. 117, 2638–2648 (2007) |
 | Genomics: Gene expression in the worm
The transparent body of Caenorhabditis elegans and its well known and complete cellular lineage description permits researchers to undertake large-scale gene expression studies in vivo.
Original research paper: PLoS Biol. 5, 1981–1997 (2007) |
 | Fungal virulence: Salvageable research
The enzymes and pathways responsible for nicotinamide adenine dinucleotide (NAD+) biosynthesis from nicotinic acid (NA), nicotinamide (NAM) and nicotinamide riboside (NR) precursors have been fully delineated in the fungal pathogen Candida glabrata.
Original research paper: Mol. Microbiol. 66, 14–25 (2007) |
 | Cell division: Fractal cycling
Ca2+/calmodulin-dependent kinase-II (CaMKII) is activated by the rapid transient increase in cytoplasmic Ca2+ that follows fertilization of Xenopus eggs, eventually leading to cyclin degradation and oocyte cell arrest in the metaphase of meiosis II.
Original research paper: Nature 449, 336–340 (2007) |
 | Innate immunity: TLR3: rising above redundancy
A Toll-like receptor 3 (TLR3) deficiency in two children with herpes simplex virus type 1 (HSV1) encephalitis (HSE) has helped researchers identify TLR3 deficiency as the second genetic etiology of isolated HSE.
Original research paper: Science 317, 1522–1527 (2007) |
 | Tumorigenesis: A shocking enabler of tumour growth
The transcription factor heat-shock factor 1 (HSF1), which mediates the conserved heat-shock response that allows cells to adapt to stress, also has an opposite role in cancer where it promotes tumorigenesis.
Original research paper: Cell 130, 1005–1018 (2007) |
 | Tumorigenesis: Size is everything
The mammalian homologue of Yorkie (Yki) — a transcriptional co-activator involved in the Hippo pathway that suppresses tissue growth in Drosophila — has been found to regulate organ size in mice.
Original research paper: Cell 130, 1120–1133 (2007) |
 | Ion channels: Spicing up local anaesthetics
The lidocaine derivative QX-314 was successfully used together with capsaicin to influence transient receptor potential vanilloid 1 (TRPV1) channel opening, thus providing a new approach for the development of anesthetics that numb pain without affecting other types of neurons.
Original research paper: Nature 449, 607–610 (2007) |
 | Cancer: Multiple targets to tackle tough tumours
Multiple receptor tyrosine kinases (RTKs) have been found to be co-activated in untreated glioblastoma multiforme (GBM) brain tumors, suggesting that combinations of RTK inhibitors may be useful as a strategy for GBM treatment.
Original research paper: Science 318, 287–290 (2007) |
