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.
 | Wnt signaling: Chibby blocks wingless armadillo
A novel nuclear protein, Chibby, binds to ß-catenin in competition with the transcription factor Tcf/Lef, thereby acting as an antagonist of the Wnt/Wingless signaling pathway.
Original research paper: Nature 422, 905 – 909, (2003) |
 | Development: Jaguar driven
In Drosophila, the adaptor protein Miranda is localized to the apical cortex before the basal crescent forms, and requires a motor protein, myosin VI Jaguar (Jar), to target it to the basal site.
Original research paper: Dev. Cell 4, 273 – 281, (2003) |
 | In brief: April 2003: Part 1
Signal Transduction | Immunotherapy | Synaptic plasticity | Sensory Systems | Stroke |
 | In brief: April 2003: Part 2
Adhesion | Dendritic Cells | Tumour Supressors | Cell Biology of the Neuron | Anticancer Drugs | Anticancer Drugs |
 | Organelle trafficking: Breakdown to arrive
Transport-machinery breakdown can actually be essential for cellular organelles to reach their final destination.
Original research paper: Nature 422, 87 – 92, (2003 February 16) |
 | T-cell activation: Survival of the fittest
Studies show that only T cells that get a long enough and/or strong enough stimulation are fit enough to survive and go all the way in vivo.
Original research paper: Nature Immunol. 4, 361 – 365, (17 March 2003) |
 | Tumour suppressors: Sticky situation
Loss of the intercellular contact structures known as adherens junctions can contribute to tumor invasiveness.
Original research paper: Cell 112, 673 – 684, (2003) |
 | Oncogenes: Receptor relay
c-CBL — a ubiquitin ligase that is known to be a regulator of epidermal growth-factor receptor endocytosis — is involved in an oncogenic signaling relay.
Original research paper: Proc. Natl Acad. Sci. USA 100, 2438 – 2443, (25 Feb 2003) |
 | Cell biology of the neuron: Poles apart
The neuronal membrane protein vesicle-associated membrane protein 2 (Vamp2) is eliminated from the dendritic membrane by selective retention, whereas carriers containing neuron–glia cell adhesion molecule (NgCAM) are prevented from fusing with the dendritic plasma membrane.
Original research paper: Neuron 37, 611 – 624, (2003) |
 | Lead discovery: Get a grip
Nonpeptidic inhibitors of the cysteine protease caspase-3, a key mediator of apoptosis, have been generated with the use of a novel extension of dynamic combinatorial chemistry (DCC).
Original research paper: Nature Biotech. 21, 308 – 314, (2003) |
 | Structure-based drug design: An ACE surprise
Surprisingly, the three-dimensional structure of angiotensin converting enzyme (ACE) bears little resemblance to carboxypeptidase A, and instead resembles rat neurolysin and Pyrococcus furiosus carboxypeptidase.
Original research paper: Nature 421, 551 – 554, (2003) |
 | VEGF: TIMPering with angiogenesis
Tissue inhibitor of metalloproteinases-3 (TIMP3) has a novel function independent to its matrix metalloproteinase (MMP)-inhibitory properties: it blocks the binding of VEGF to VEGF receptor-2, thereby inhibiting downstream signaling and angiogenesis.
Original research paper: Nature Medicine 9, 407 – 415, (2003) |
 | DNA recombination: A pushy protein
Rad54's job in vivo could be to remodel chromatin and clear the DNA of nucleosomes while the recombinational repair machinery searches for homologous sequences.
Original research paper: Nature Struct. Biol. 10, 182 – 186, (2003) |
 | Viral transmission:
Deadly contact
Human T-cell lymphotropic virus type 1 (HTLV-I) is transmitted across cell–cell junctions after polarizing the cytoskeleton of the infected cell at sites of cell–cell contact.
Original research paper: Science 299, 1713 – 1716, (2003) |
 | Immunodeficiency: Targeting WASP
The T-cell signaling defect that is associated with Wiskott-Aldrich syndrome (WAS) can be improved by gene therapy.
Original research paper: Blood 101, 2159 – 2166, (2003) |
 | Tumour suppressors: Ever-decreasing effects
A series of p53 hypomorphs created by stable RNA interference produces distinct tumor phenotypes in vivo.
Original research paper: Nature Genet. 33, 396 – 400, (2003) |
 | Chemical genetics: Combichem leads for asthma
A novel molecule, PNRI-299, inhibits activator protein-1 and Ref-1, and reduces the inflammation associated with asthma.
Original research paper: Proc. Natl Acad. Sci. USA 100, 1169 – 1173, (2003) |
 | Wnt signaling and neural development: Derailed but on track
Derailed, an atypical receptor tyrosine kinase present on neuronal growth cones, acts as an axon guidance receptor in conjunction with Wnt5 to direct growing axons on the correct commissure track.
Original research paper: Nature 422, 583 – 588, (10 April 2003) |
 | Chromatin:
A fork load
A dominant-negative mutant of the p150CAF-I subunit of the heterotrimeric chromatin-assembly factor CAF-I inhibits CAF-I-dependent chromatin assembly in an in vitro assay.
Original research paper: Mol. Cell 11, 341 – 351, (2003) |
 | Plant development:
Channelling elongation
New research has pinpointed the production of reactive oxygen species (ROS) by an NAPDH oxidase in the activation of Ca2+ channels in elongating root cells.
Original research paper: Nature 422, 442 – 446, (2003) |
 | Innate immunity:
Living without Toll-like receptors
The main Toll-like receptor signal-transduction pathway in humans is not essential for survival and has a much narrower role than expected.
Original research paper: Science 299, 2076 – 2079, (13 March 2003) |
 | Chemoprevention:
Acting on active AKT
Deguelin — a natural plant product drug — inhibits activated AKT in an in vitro lung carcinogenesis progression model system, so showing potential as a lung cancer chemoprevention agent.
Original research paper: J Natl Cancer Inst 95, 291 – 301, (2003) |
 | Therapeutic proteins:
Polymer-perfect proteins
Researchers have now used total chemical synthesis to produce a homogeneous population of a monodisperse polymer-modified synthetic erythropoiesis protein (SEP), a version of the highly successful protein drug human erythropoetin (Epo).
Original research paper: Science 229, 884 – 887, (2003) |
 | Protein folding diseases:
Raising the bar
For the first time, small-molecule inhibitors have been shown to stop protein-folding diseases before they begin.
Original research paper: Science 299, 713 – 716, (2003) |
 | Phosphoinositide signaling: Willing and c-Abl
A novel functional interdependence between c-Abl tyrosine kinase and phosphoinositide signaling via phospholipase C-?1 has been shown, revealing bidirectional regulation of lipid signaling pathways and Abl tyrosine kinases.
Original research paper: Nature Cell Biology 5, 309 – 319, (2003) |
 | Cell cycle:
A way out
Cells must be able to reverse the state of mitotic exit to enter the next cell cycle, and a report in Cell now gives a new insight into just how cells do this.
Original research paper: Cell 112, 697 – 709, (2003) |
 | Signalling:
New Polo player
A 'polo-box domain', a new phosphoserine/phosphothreonine-binding domain, is present in the mitotic kinase Polo-like kinase 1.
Original research paper: Science 299, 1228 – 1231, (2003) |
 | Lymphocyte development:
Mint- flavoured B cells
A nuclear inhibitor of Notch signalling has now been identified, which is the first described mammalian functional equivalent of Hairless.
Original research paper: Immunity 18, 301 – 312, (2003) |
 | Prognostic markers:
Two are worse than one
Overexpression of an oestrogen receptor co-activator, AIB1, together with high expression of a member of the epidermal growth-factor-receptor family, ERBB2, in oestrogen-positive breast cancer patients is associated with resistance to tamoxifen.
Original research paper: J Natl Cancer Inst 95, 353 – 361, (2003) |
 | Oncogenesis:
Winging your way to cancer with wingless
Loss of Wnt1, even in advanced cancer, can result in tumour regression.
Original research paper: Genes Dev. 17, 488 – 501, (2003) |
 | Development:
Head start
Secreted factor Coco appears to fulfil the properties of a maternally expressed mesoderm inhibitor.
Original research paper: Development 130, 1381 – 1389, (2003) |
