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.
 | Immunology: Toll-like receptor 3 signaling enables cross-priming
Dendritic cells use Toll-like receptor 3 to promote cross-priming of cytotoxic T cells (CTLs) against virally infected cells.
Original research paper: Nature 433, 887 – 892, (24 February 2005) |
 | DNA Repair:
Breaking up is hard to do
New insight has been given into the mechanim by which DNA double-strand breaks (DSBs) are held together during DNA repair.
Original research paper: Curr. Biol. 14, 2096 – 2106, (2004) |
 | In brief: February 2005
Proteomics | Mitosis | Signalling | Cytoskeleton | Chemokines | Dendritic | Prognosis | Cancer stem cells | Stem cells | Evo–Devo | Gene expression | Neural induction | Neurodegenerative disease | Screening | Infectious diseases | Virology | Imaging and Visualization | DNA Cloning and Amplification | Genomics |
 | Calcium:
A changed cameleon
A new and improved genetically encoded fluorescent sensor that can monitor Ca2+-concentration fluctuations in the ER (Ca2+
ER) has just been developed.
Original research paper: Proc. Natl Acad. Sci. USA 101, 17404 – 17409, (2004) |
 | Inflammation:
RIP2 leaves calling card for Crohn's disease
The cytoplasmic protein nucleotide-binding oligomerization domain 2 (NOD2) is involved in the inflammatory immune response to the commensal gut bacteria that causes Crohn's disease.
Original research paper: Curr. Biol. 14, 2217 – 2227, (2004) |
 | Carcinogenesis:
Catch-22
The pro-apoptotic protein BCL2 has now been shown to also stimulate mutagenesis through its independent function in cell-cycle arrest, by suppressing DNA repair.
Original research paper: Nature Cell Biol. 7, 137 – 147, (2004) |
 | When DNA alone just is not enough
Hybrids made of a triplex-forming oligonucleotide (TFO) and a translocation peptide have now been developed, which can effectively penetrate the plasma and nuclear membranes of a cell leading to mutagenesis or site-directed recombination.
Original research paper: Nucleic Acids Res. 32, 6595 – 6604, (2004) |
 | Bacterial pathogenesis: Pneumococcus forks out...
New research provides a first molecular insight into how Streptococcus pneumoniae binds to and invades human epithelial cells
Original research paper: EMBO J. 24, 34 – 43, (2004) |
 | JNK signaling: c-Abl’s deadly shuttle to the nucleus
c-Jun N-terminal kinase (Jnk) phosphorylation of 14-3-3 proteins regulates the nuclear targeting of the tyrosine kinase c-Abl, in response to DNA damage.
Original research paper: Nature Cell Biology , (6 February 2005) |
 | Epigenetics:
Erasing the mark
The first histone lysine demethylase — an enzyme that removes the methyl group from histone tails — has just been identified.
Original research paper: Cell 119, 941 – 953, (2004) |
 | Signalling:
Friendly rivalry
A new non-enzymatic way of phosphorylating involving inositol pyrophosphates has been discovered.
Original research paper: Science 306, 2101 – 2105, (2004) |
 | Autoimmunity:
TLR signals provide the missing factor
Toll-like receptor (TLR) ligation is required for the destruction of pancreatic islet β-cells by autoreactive T cells in a mouse model of diabetes.
Original research paper: Nature Med. 11, 138 – 145, (2005) |
 | Regulatory T cells:
A step closer to the clinic
Two animal models of autoimmunity — type 1 diabetes and experimental autoimmune encephalomyelitis — provide insight into the therapeutic potential of regulatory T cells.
Original research paper: Diabetes 54, 306 – 310, (2005) |
 | Therapeutics:
On the TRAIL of death
Histone-deacetylase inhibitors (HDACIs) increase the expression of the death-receptor ligand TRAIL in cancer cells, leading to tumor-cell death.
Original research paper: Nature Med. 11, 71 – 76, (2005) |
 | Epigenetics:
Breaking the silence
Cells use a dynamic process that regulates the balance between silent heterochromatin and active euchromatin as a way of shutting off gene expression.
Original research paper: Genes Dev. 18, 2973 – 2983, (2004) |
 | Neurodegenerative disorders:
Hunting glycoproteins
The complete set of the main brain glycoproteins has just been characterized in an attempt to uncover any defects in the glycosylation process that lead to neurodegenerative disorders.
Original research paper: Eur. J. Neurosci. 20, 3489 – 3497, (2004) |
 | Structure-Based Drug Design:
Seeking selectivity
The goal of designing isoform-selective phosphodiesterase (PDE) inhibitors with improved potency and fewer side effects has been brought one step closer following the recent publication of high-resolution crystal structures of PDEs bound to a selection of inhibitors.
Original research paper: Structure 12, 2233 – 2247, (2004) |
 | Measuring a bacteria's sweet tooth
After DNA and protein chips, here come the carbohydrate microarrays capable of detecting and classifying bacteria based on their sugar binding affinities.
Original research paper: Chem. Biol. 11, 1701 – 1707, (2004) |
 | Alternatives to a horse
Synthetic receptors give cells new abilities to take up foreign molecules.
Original research paper: J. Am. Chem. Soc. 126, 16379 – 16386, (2004) |
 | Signalling:
A pick-me-up
Src becomes activated during transit from the perinuclear region to the plasma membrane in a process that involves the actin cytoskeleton and the small GTPase RhoB.
Original research paper: Dev. Cell 7, 855 – 869, (2004) |
 | BDNF signaling: cAMP is the gate to well-formed spines
Cyclic-AMP regulates brain–derived neurotrophic factor (BDNF) function in mature hippocampal neurons by modulating TrkB phosphorylation and trafficking.
Original research paper: Nature Neuroscience 8, 164 – 172, (2005) |
 | Nuclear transport:
How to get out
The 2.0-Å resolution crystal structure of a nuclear export complex comprising RanGTP, Cse1 and Kap60 provides insight into the role of RanGTP in nuclear protein export.
Original research paper: Nature 432, 872 – 877, (2004) |
 | T-cell signalling:
DRAK2 puts the brakes on T-cell responses
Death-associated protein-kinase-related 2 (DRAK2) when overexpressed induces apoptosis, however mice deficient in DRAK2 do not show defects in apoptosis; instead their T cells are hypersensitive to stimulation through the T-cell receptor (TCR).
Original research paper: Immunity 21, 781 – 791, (2004) |
 | Oncolytic viruses:
Export license
A new microfluidic device allows fluorescence-activated cell sorting (FACS) of as few as 1,000 mammalian cells to high purity and with efficient yields.
Original research paper: Cancer Cell 6, 611 – 623, (2004) |
 | Cancer genetics:
Tumour-suppressor super models
Two new mouse models that closely resemble LiFraumeni syndrome shed light on why the TP53 mutations seen in a wide range of human cancers are so oncogenic.
Original research paper: Cell 119, 861 – 872, (2004) |
 | Genome stability:
Assembling the repair kit
A new analysis has filled in some important gaps in the knowledge of how the human genome repairs the double strand breaks (DSBs) in DNA that are induced by ionizing radiation (IR).
Original research paper: Mol. Cell 16, 715 – 724, (2004) |
 | Neurodegenerative disorders:
Fluid dynamics
An investigation of the effects of neuronal membrane cholesterol levels on the production of the amyloid-β (Aβ) peptide has resolved some of the paradoxes associated with cholesterol-lowering drugs and neurodegeneration.
Original research paper: J. Cell Biol. 167, 953 – 960, (2004) |
 | Lead Optimization:
Improving natural strength
A new and efficient method for genetically manipulating the chemical structure of natural products has been developed, and its success shown in the modification of a polyketide natural product that might provide the basis for the development of potent anticancer agents.
Original research paper: Chem. Biol. 11, 1625 – 1633, (2004) |
 | FACS-on-a-chip
The engineered oncolytic adenovirus ONYX-015 inactivates p53 by altering RNA export pathways, thus revealing a potentially interesting therapeutic target.
Original research paper: Nat. Biotechnol. 23, 83 – 87, (2005) |
 | Innate Immunity: Signaling Crosstalk by Chromatin Remodeling
The Jnk-activated transcription factor AP1 represses the NF-κB pathway by recruiting the histone deacetylase dHDAC1 to NF-κB activated promoters.
Original research paper: Nature Immunology 6, 211 – 218, (2005) |
 | Cell cycle:
Here comes the cycling squad!
The complete set of Drosophila melanogaster protein kinases has been tested for their involvement in the cell cycle, highlighting the interconnection between these phosphorylation events and the regulation of cellular physiology.
Original research paper: Nature 432, 980 – 987, (2004) |
 | Meiosis:
Under arrest
New light has been shed on how meiotic arrest is maintained in mouse oocytes up until the time that luteinizing hormone (LH) induces the resumption of meiosis and ovulation.
Original research paper: Science 306, 1947 – 1950, (2004) |
 | Cytokines:
Identifying how IL-23 drives disease
It has now been shown that interleukin-23 (IL-23) participates in the pathogenesis of autoimmune inflammation by promoting the development of a pathogenic CD4+ T-cell population that produces IL-6, IL-17 and tumor-necrosis factor (TNF).
Original research paper: J. Exp. Med. 201, 233 – 240, (2005) |
 | T-cell development:
Orchestrating T-cell development
A new study shows that CD4+CD8+ (double positive, DP) thymocytes, which are currently thought of simply as progenitors of αβTcells, regulate the development of early progenitors and of γδT cells.
Original research paper: Science (9 Dec 2004) |
 | Oncogenes:
Addicted to MYC?
It has now been shown in mammary adenocarcinoma cells that inactivation of oncogenes such as MYC does not always reverse the malignant properties of the tumor types that have been initiated by them.
Original research paper: Cancer Cell 6, 577 – 586, (2004) |
 | Technology:
A wide (micro)array of options
Microarrays can now be used to simultaneously study gene expression and perform genotyping, as well as being highly useful in comparative genomic hybridization studies.
Original research paper: Genome Res. 15, 284 – 291, (2005) |
 | Repair:
Essential repairs
The mechanisms that lead to remyelination in the adult brain have now been shown to parallel those that occur during the development of oligodendrocytes and to involve the protein OLIG1.
Original research paper: Science 306, 2111 – 2115, (2004) |
 | A better way to pick a plum
Using a technique based on a naturally occurring process called somatic hypermutation (SHM), researchers developed mPlum – a robust and substantially red-shifted red fluorescent protein (RFP) variant.
Original research paper: Proc. Natl. Acad. Sci. USA 101, 16745 – 16749, (2004) |
 | Malaria:
Malaria secretome uncovered
A general export signal required for the secretion of Plasmodium proteins into host erythrocytes has just been identified and the 'exported proteome' or 'secretome' of the major malaria parasite has been defined.
Original research paper: Science 306, 1930 – 1933, (2004) |
 | Bacterial Physiology:
Filament formation
New research has shed light on the structure and formation of the Ftsz protofilament – a protein essential for bacterial cell division.
Original research paper: Nature Struct. Mol. Biol. 11, 1243 – 1250, (2004) |
