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.
 | RanGTP gradient: Cargo liberator and microtubule regulator
A biosensor of the RanGTP-dependent release of nuclear cargoes is used to examine the functional significance of the RanGTP gradient.
Original research paper: Nature 440, 697 – 701 (30 March 2006) |
 | PCNA monoubiquitination: USP1 regulates Translesion DNA synthesis
The deubiquitinating enzyme USP1 autocleaves upon UV irradiation, causing the accumulation of monoubiquitinated PCNA and the subsequent localization of Polη to DNA repair foci.
Original research paper: Nature Cell Biology 8, 341 - 347 (2006) |
 | NFAT regulation: DYRK kinases prime inhibition
A genome-wide RNAi screen in Drosophila identifies the kinases DYRK1A and DYRK2 as negative regulators of NFAT in vertebrates.
Original research paper: Nature 441, 646 - 650 (01 Jun 2006) |
 | Dorso-ventral polarity: AChordin to Sizzled
Interaction between Sizzled, Chordin and the novel Tolloid metalloproteinase Bmp1a regulates dorso-ventral axis formation in Zebrafish embryos.
Original research paper: Nature Cell Biology 8, 329 - 340 (2006) |
 | Cytokine trafficking: Two exit strategies
Activated T helper cells secrete cytokines through two directionally and molecularly distinct pathways.
Original research paper: Nature Immunology 7, 247 – 255 (2006) |
 | Fine tuning
The scaffold protein Ste5 not only functions as an interaction assembly point for the mating-pathway components in yeast, it also modulates signaling output.
Original research paper: Science 6, 827 – 837, (19 Jan 2006) |
 | IFNα tips the balance towards APOBEC3G
Interferon-α (IFNα) increases the expression of APOBEC3G, an enzyme shown to induce the degradation of HIV DNA, leading to a marked decrease in HIV replication.
Original research paper: J. Exp. Med. 203, 41 – 46, (2006) |
 | In brief: March 2006
Ageing | Technology | Development | Small RNAs | Autoimmunity | T cells | Neuroimmunology | Targeted therapy | Metastasis | Gene expression | Technology | Development | Sensory systems |
 | Early warning
A subset of dendritic cells secrete high levels of interferon-y (IFNy) and mediate tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-dependent lysis of tumor cells.
Original research paper: Nature Med. (29 Jan 2005) |
 | MicroRNAs mediate synapse development
miR-134 is a brain-specific microRNA that negatively regulates the size of dendritic spines — postsynaptic sites of excitatory synaptic transmission — in rat hippocampal neurons.
Original research paper: Nature 439, 283 – 289, (2006) |
 | PAK up your troubles
Loss of PAK (p21-activated kinase) activity in the brains of patients with Alzheimer's disease (AD) could be linked to the cognitive defects observed in AD.
Original research paper: Nature Neurosci. 9, 234 – 242, (2006) |
 | Single-cell breast implants
Two groups have independently isolated mouse mammary stem cells, definitively demonstrating their pluripotency by showing that a single cell can reconstitute an entire mammary gland in vivo.
Original research paper: Nature 439, 84 – 88, (2006) |
 | Hitching a ride
Mono-oriented chromosomes can glide toward the spindle equator along kinetochore fibers attached to bi-oriented chromosomes in a mechanism dependent upon the microtubule motor protein CENP-E.
Original research paper: Science 311, 388 – 391, (2006) |
 | The journey begins for αβ and γδ T cells
A new study reveals differences in Notch-Delta signaling dependence and gene expression at the earliest stages of divergence between developing αβ and γδ T-lineage cells.
Original research paper: Immunity 24, 53 – 64, (2006) |
 | Culpable kinase
The ability of cyclin D1 to activate cyclin-dependent kinase CDK4 underlies the critical role for cyclin D1 in breast cancer formation.
Original research paper: Cancer Cell 9, 23 – 32, (2006) |
 | Making steps in stroke therapy
Three independent studies describe new models of stroke and potential strategies for the development of therapeutic agents that reduce neurodegeneration after ischemia.
Original research paper: Proc. Natl Acad. Sci. USA 103, 1581 – 1586, (2006) |
 | Influenza vaccines
A series of small-molecule inhibitors that prevent the association of p53 with its coactivator, the histone acetyltransferase p300/Creb-binding protein (CBP), are able to downregulate the p53-mediated response to DNA damage.
Original research paper: Eur. Respir. J. 17, 1282 – 1293, (2004) |
 | A quick fix for avian influenza?
A recombinant DNA vaccine based on an adenovirus vector represents an alternative strategy against the threat of an H5N1avian influenza virus pandemic.
Original research paper: J. Virol. 80, 1959 – 1964, (2006) |
 | ER stress induces systemic inflammation
Cleavage of the transcription factor CREBH upon endoplasmic reticulum (ER) stress initiates an acute-phase systemic inflammatory response.
Original research paper: Cell 124, 587 – 599, (2006) |
 | A flying start
A new study links the Notch?Delta pathway with epigenetic silencing pathways and cell-cycle control during tumorigenesis in the Drosophila eye.
Original research paper: Nature 439, 430 – 436, (2006) |
 | Why crawl when you can leap?
Most cases of cardio-facial-cutaneous syndrome are caused by sporadic missense mutations in BRAF or MAP2K1/MAP2K2 — two transducers of MAPK signaling.
Original research paper: Science 63, 423 – 426, (26 January 2006) |
 | More than a flicker
A novel fluorescence quenching technique provides compelling evidence that 'kiss-and-run' is the main mode of vesicle fusion at hippocampal synapses.
Original research paper: Neuron 49, 243 – 256, (2006) |
 | To Start or not to Start?
By monitoring fluorescent protein reporters during cell division, researchers suggest that multiple pathways may independently suppress different kinds of noise at the start of the cell cycle in budding yeast.
Original research paper: Mol. Cell 21, 3 – 14, (2006) |
 | A modern modification
Methylglyoxal, a highly reactive a-oxoaldehyde produced during glycolysis, post-translationally modifies the co-regulator protein mSin3A leading to an increase in angiopoietin-2 expression.
Original research paper: Cell 124, 275 – 286, (2006) |
 | Recognition of cytosolic DNA
Macrophages recognize foreign cytosolic DNA through a novel interferon regulatory factor (IRF)-3-dependent pathway that triggers a potent type I interferon response.
Original research paper: Immunity 24, 93 – 103, (2006) |
 | Armed for action
Blocking the interaction between PD1 (programmed death 1) and its ligand PDL1, reverses the functional impairment of exhausted T cells and reduces the viral load in mice infected with lymphocytic choriomeningitis virus (LCMV).
Original research paper: Nat. Biotechnol. 24, 205 – 209, (2006) |
 | Affinity for enhancer prediction
A high-throughput method for determining the DNA-binding specificities of transcription factors used in conjunction with a computational tool that predicts novel mammalian enhancer locations will facilitate the characterization of temporal and spatial patterns of gene expression.
Original research paper: Cell 124, 47 – 59, (2006) |
 | Eye catching
During development of the Drosophila visual system, retinal axons release Hedgehog to induce laminar neuron differentiation and synaptogenesis.
Original research paper: Development 125, 3753 – 3764, ( 2006) |
 | Immunomodulators::
Reversing exhaustion
Blocking the interaction between PD1 (programmed death 1) and its ligand PDL1, reverses the functional impairment of exhausted T cells and reduces the viral load in mice infected with lymphocytic choriomeningitis virus (LCMV).
Original research paper: Nature 439, 682 – 687, (2006) |
 | Type III secretion:
Expert mimics
A large family of bacterial type III secreted effectors that mimic the functions of members of the Rho family of small GTPases has been identified in several Gram-negative pathogens.
Original research paper: Cell 124, 133 – 145, (2006) |
 | Restricting the spreading
Studies using Drosophila embryos show that lipid modification limits the secretion of Hedgehog (Hh), its multimerization and its long-range signaling activity.
Original research paper: Development 133, 407 – 418, (2006) |
 | MKP1 — a dynamic immune regulator
Four independent papers show that MAPK phosphatase 1 (MKP1) is a key negative regulator of Toll-like receptor (TLR)-induced inflammation in vivo.
Original research paper: Proc. Natl Acad. Sci. USA 103, 2274 – 2279, (2006) |
 | Disruptive influence
A new mouse model of pancreatic cancer suggests that disruption of the transforming growth factor-beta (TGFß) signaling pathway leads to the development of premalignant lesions.
Original research paper: Proc. Natl Acad. Sci. USA 103, 1858 – 1863, (2006) |
 | The open secret of pluripotentiality
Hyperdynamic binding of structural chromatin proteins may contribute to the maintenance of plasticity in undifferentiated embryonic stem cells.
Original research paper: Dev. Cell 10, 105 – 116, (2006) |
 | Another role for leptin?
Leptin, a hormone secreted from adipose tissue that helps to regulate body weight, also attenuates depression-like behavior in rats.
Original research paper: Proc. Natl Acad. Sci. USA 103, 1593 – 1598, (2006) |
 | Search party
New assays for the rapid analysis of transcription factor binding site preferences, in combination with a simple yet powerful computational genomic analysis tool, could yield a bounty of valuable data.
Original research paper: Cell 124, 47 – 59, (2006) |
