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.
 | Tumor angiogenesis: Better vessels, better therapy
Rgs5-mediated inhibition of G-protein signaling results in a more mature tumor vasculature, which increases the effectiveness of T-cell immunotherapy in tumors.
Original research paper: Nature 453, 410-414 (2008) |
 | TNF signaling: The long run to arthritis
Tumor necrosis factor (TNF) stimulation primes macrophages for higher inflammatory responses through an interferon-response factor 1 (IRF1-) and interferon β- (IFN-β-)mediated autocrine loop similar to that used by toll-like receptors (TLRs).
Original research paper: Nat. Immunol. 9, 378-387 (2008) |
 | Aging: Notching up stem cell differentiation
A mutant form of lamin A activates the Notch signaling pathway to promote precocious mesenchymal stem cell differentiation.
Original research paper: Nature Cell Biology 10, 452-459 (2008) |
 | Tumorigenesis: eNOS is enough
Oncogenic KRas initiates and maintains tumor growth by stimulating the PI3K–AKT–eNOS signaling pathway, which activates wild-type HRas and NRas.
Original research paper: Nature 452, 646-649 (2008) |
 | Apoptosis: Killing neutrophils the cathepsin way
Cathepsin D directly cleaves and activates caspase-8 at the beginning of a pro-apoptotic pathway in neutrophils, showing how apoptosis can be activated in the absence of death-receptor ligation.
Original research paper: J. Exp. Med. 205, 685-698 (2008) |
 | T-cell activation: Polarity and CRTAM: a matter of timing
Researchers have described a previously unrecognized late phase of cell polarity in some CD4+ T cells that is controlled by CRTAM (MHC-class-1-restricted T-cell-associated molecule), and regulates interferon-γ (IFN-γ) and interleukin-22 (IL-22) production.
Original research paper: Cell 132, 846-859 (2008) |
 | In brief: April 2008
Cytoskeleton | Regulatory T cells | T cells | Innate immunity | Tumour suppression | Tumorigenesis | Mechanotransduction | Genetic screens | Molecular neuroscience | Analgesia | Anticancer drugs | Microscopy | Imaging and visualization |
 | Radiation therapy: Sensitizing stem cells
A new study has shown that although radiation therapy causes apoptosis in proliferating medulloblastoma cells, it only induces cell-cycle arrest in medulloblastoma stem cells; however, this difference can be diminished using a small-molecule inhibitor.
Original research paper: Genes Dev. 22, 436-448 (2008) |
 | Tumorigenesis: A marked CARD
The cytoplasmic scaffolding protein CARD11 contains mutations that can constitutively induce nuclear factor κB (NFκB) activation in the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL).
Original research paper: Science 319, 1676-1679 (2008) |
 | Neurodegenerative disease: Capturing MS targets
Large-scale proteomic profiling of multiple sclerosis lesions (or 'plaques') in the central nervous system is useful for identifying new drug targets for this disease.
Original research paper: Nature 451, 1076-1081 (2008) |
 | Imaging and visualization: Protein suicide highlights the cell cycle
By exploiting the process of regulated protein death, researchers have created a new class of fluorescent sensors that highlight cell-cycle transitions in living cells.
Original research paper: Cell 132, 487-498 (2008) |
 | Innate immunity: Detecting DNA via the inflammasome
Activation of the inflammasome, a protein complex involved in the innate immune response against many pathogens, has been found to also be important for an effective inflammatory response to DNA viruses.
Original research paper: Nature 452, 103-107 (2008) |
 | Apoptosis: BIM and FAS: the ultimate death squad
Three studies have shown that the cell-extrinsic (BIM-induced) and cell-intrinsic (FAS-induced) pathways cooperate to maintain homeostasis, prevent autoimmunity and terminate immune responses.
Original research paper: Immunity 28, 197-205 (2008) |
 | Tumour suppressors: Spread your wings
The E2F1 transcription factor has been identified as an oncogenic target of the Salvador (SAV)–Warts(WTS)–Hipp(HPO) tumor suppressor pathway.
Original research paper: Curr. Biol. 18, 435-441 (2008) |
 | DNA repair: A major Ku?
Binding of the oncogene BCL2 to the DNA repair protein Ku appears to block both the Ku–DNA interaction and DNA protein kinase recruitment, thus inhibiting DNA repair.
Original research paper: Mol. Cell 29, 488-498 (2008) |
 | Learning and memory: Cease or persist?
In rat memory rescue experiments, brain-derived neurotrophic factor (BDNF) was found to be sufficient to confer persistence to long-term memories through its effects on ERK activity.
Original research paper: Proc. Natl Acad. Sci. USA 105, 2711-2716 (2008) |
 | Psychiatric disorders: Double GPCR trouble
The potential and confirmed anti-psychotic drug targets metabotropic type-2 glutamate receptor (mGluR2) and 5-hydroxytryptamine 2A receptor (5-HT2AR) have been found to form a complex that might be involved in schizophrenia.
Original research paper: Nature 452, 93-97 (2008) |
 | Membrane trafficking: GTPases stack up
The GTPases RAB6 and ARL1 form an unusual tetrameric complex that jointly localizes the GCC185 tether protein at the trans-Golgi network (TGN).
Original research paper: Cell 132, 286-298 (2008) |
 | Innate immunity: TLR4 signalling
The TIRAP–MyD88 and TRAM–TRIF signaling pathways are induced sequentially, with the TRAM–TRIF pathway only being operational from early endosomes following Toll-like receptor 4 endocytosis.
Original research paper: Nature Immunol. 9, 361-368 (2008) |
 | Tumorigenesis: Turning the hands of time
The discovery of a link between DNA damage response (DDR) signaling and the scheduling of circadian rhythms may help us discover why there is an increase in tumorigenesis when circadian rhythms are altered.
Original research paper: Curr. Biol. 18, 286-291 (2008) |
 | Olfactory processing: Lighting up the path to romance
The neural circuit activated by the pheromone cis-vaccenyl acetate (cVA) differs subtly between males and females, explaining how it can both suppress and promote mating with males in Drosophila males and females, respectively.
Original research paper: Nature 452, 473-477 (2008) |
 | Plant disease resistance: Chloroplast protein gets guarded
It has been found that following the infection of a plant with the tobacco mosaic virus (TMV), the viral helicase protein and a chloroplast protein form a complex that is recognized by a plant immune receptor.
Original research paper: Cell 132, 449-462 (2008) |
 | Nuclear transport: Signalling and transport converge
RSK- and AKT-mediated phosphorylation of Ran-binding protein-3 (RanBP3) increases the efficiency of nuclear import.
Original research paper: Mol. Cell 29, 362-375 (2008) |
 | Antiviral immunity: Re-routing the interferon response through B cells
Mouse cytomegalovirus infection induces expression of IFNα/β via a lymphotoxin β receptor (LTβR)–NF-κB signaling pathway.
Original research paper: Cell Host Microbe 3, 67-76 (2008) |
 | Metastasis: A metastatic switch
Upregulation of SATB1 — a genome organizer that controls chromatin structure and the expression of multiple genomic loci — in breast cancer cells correlates with aggressive tumor phenotypes and shorter patient survival time.
Original research paper: Nature 452, 187-193 (2008) |
 | Addiction: Damping down alcohol dependence
Alcohol cravings are suppressed by pharmacological inhibition of the stress and anxiety response mediator neurokinin 1 receptor (NK1R), thus providing a biological explanation for the link between stress and alcoholism relapse.
Original research paper: Science 319, 1536-1539 (2008) |
 | Chemical biology: DNA synthesis lights up
Researchers have developed a method for detecting DNA synthesis in proliferating cells that uses small-molecule fluorophores rather than antibodies, which improves resolution and signal strength.
Original research paper: Proc. Natl. Acad. Sci. USA 105, 2415-2420 (2008) |
