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.
 | Cell senescence: Under arrest
A positive feedback loop between reactive oxygen species (ROS) and protein kinase Cδ (PKCδ) cooperates with the retinoblastoma tumor suppressor pathway to irreversibly arrest senescent cells.
Original research paper: Nature Cell Biology 8, 1291-1297 (2006) |
 | Neutrophil signaling: Integrin and Syk in an adaptor-coupled ITAM
The phosphorylation of adaptors containing the immunoreceptor tyrosine-based activation motif (ITAMs) by Src kinases is the first intracellular step of integrin signaling in neutrophils and macrophages.
Original research paper: Nature Immunology 7, 1326-1333 (2006) |
 | RTK/ERK signaling: Proximal effectors revealed
A functional RNAi screen designed to isolate proximal effectors of RTK signaling has uncovered novel regulators, many of which have functions assigned in other pathways.
Original research paper: Nature 444, 230-234 (9 November 2006) |
 | Retinoblastoma: Adding p53 to the mix
Retinoblastomas amplify inhibitors of the p53 signaling pathway leading to cell survival and tumor progression.
Original research paper: Nature 444, 61-66 (2 November 2006) |
 | Walking the integrin activation road
The GTPase Rap1 mediates protein kinase C activity to induce the formation of an 'integrin activation complex' that binds to and activates integrin receptors.
Original research paper: Curr. Biol. 16, 1796 – 1806, (2006) |
 | Therapy: Barking up the right tree
Pericytes and the vascular basement membrane can aid blood vessel re-growth in tumors after vascular growth factor inhibitor administration has been stopped.
Original research paper: J. Clin. Invest. 116, 2610 – 2621, (2006) |
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In brief: November 2006
Membrane trafficking | DNA repair | Mechanisms of disease | Inflammation | Viral immunity | Signaling | Viral immunity | Chemoresistance | Breast cancer | Tumor microenvironment | Development | Synaptic physiology | Small RNAs | Cloning |
 | Depression gene in action
A tendency to anxiety-related temperaments and depression in humans is related to the length of serotonin transporter gene (5-HTT) alleles.
Original research paper: Proc. Natl Acad. Sci. USA. 7, 818 – 827, (9 October 2006) |
 | Enigmatic enzyme
New findings have provided the first evidence of multiple ligand-binding to Cytochrome P450 (CYP) 3A4 and revealed the flexibility of the enzyme ligand-binding site, thus complicating any computational ligand-binding models of this enzyme.
Original research paper: Proc. Natl Acad. Sci. USA 103, 13682 – 13687, (2006) |
 | Story of C's
Chromosome conformation capture (3C) graduates to a tool for mapping interaction networks, thanks to a clever way of making molecular 'carbon copies'.
Original research paper: Genome Res. 16, 1299 – 1309, (2006) |
 | Fatal cut
Proteolysis of autophagy-related gene-5 (ATG5) protein has been shown to switch cellular fate from autophagic cell death to apoptosis.
Original research paper: Nature Cell Biol. 8, 1124 – 1132, (2006) |
 | TLRs doing it for themselves
Toll-like receptor (TLR)-mediated recognition of the parasite antigen profilin provides an additional mechanism by which TLR signaling can influence the adaptive immune response.
Original research paper: Immunity 25, 655-664 (2006) |
 | Leukaemia Stem Cells: Homing in on CD44
CD44 is required for the homing and engraftment of leukemic stem cells but not hematopoietic stem cells, making it a possible therapeutic target for leukemia.
Original research papers: Nature Medicine 12, 1167 - 1174 (2006); Nature Medicine 12, 1175 - 1180 (2006); |
 | Epigenomics: The first genome-wide methylome
Almost 19% of the A. thaliana genome is methylated, and besides the expected degree of methylation in heterochromatin, a considerable amount is also found in euchromatin.
Original research paper: Cell 126, 1189 – 1201, (2006) |
 | Folding away the bad guys
Huntingtin (HTT) has been identified as a new substrate for the chaperone TRiC, which can direct HTT away from forming the toxic aggregates that characterize the pathology of Huntington's disease.
Original research paper: Nature Cell Biol. 8, 1163 – 1169, (2006) |
 | Downstream GPCR inhibition
BIM-46174 is a novel anticancer agent that selectively inhibits the heterotrimeric G-protein subunit complex, overcoming the limitations of many G-protein coupled receptor (GPCR) inhibitors that are only able to inhibit one GPCR.
Original research paper: Cancer Res. 66, 9227 – 9234, (2006) |
 | A protein alternative to RNAi
A general method of targeting tagged proteins for rapid degradation in the cell promises to provide a powerful alternative to RNA interference (RNAi) for studying the functions of proteins in living cells.
Original research paper: Cell 126, 995 – 1004, (2006) |
 | You lose some, you gain some
New studies shed light on the mechanism by which the endoplasmic reticulum signals Ca2+ depletion to the plasma membrane.
Original research paper: Nature 443, 226 – 229, (2006) |
 | Ubiquitylation gives DCs the professional edge
Ubiquitylation downregulates the cell-surface expression of MHC class II molecules during the maturation of dendritic cells.
Original research paper: Nature 177, 341 – 354, (8 Oct 2006) |
 | Positive feedback
The tumor suppressor LATS2 interacts with MDM2, a key negative regulator of the tumor suppressor p53, to promote p53 activation after damage to the mitotic spindle.
Original research paper: Genes Dev. 20, 2687 – 2700, (2006) |
 | Neuroligin knockouts: form but no function
Neuroligins, a family of postsynaptic cell adhesion molecules, appear to be required for synaptic maturation and function, but not synapse formation.
Original research paper: Neuron 51, 741 – 754, (2006) |
 | Homeobox genes: eyeing the clock
Homeobox proteins can work as effectors of a cellular clock that regulates the timing of retinal cell differentiation.
Original research paper: PLoS Biol. 4, 1562-1571 (2006) |
 | Helping hand for halting inflammation
Cyclin-dependent kinase (CDK) inhibitors enhance the resolution of neutrophil-dependent inflammation by promoting inflammatory cell apoptosis.
Original research paper: Nature Med. 12, 1056 – 1064, (2006) |
 | Chemical genomics: Joining the small-molecule dots
The Connectivity Map is a new database of 453 genome-wide expression profiles produced after the treatment of human cell lines with bioactive small molecules, including a range of Food and Drug Administration (FDA)-approved drugs.
Original research paper: Science 313, 1929 – 1935, (2006) |
 | Unlocking TH17-cell differentiation
The transcription factor and nuclear hormone receptor retinoic-acid-related orphan receptor-γt (RORγt) directs the differentiation of interleukin-17-producing pro-inflammatory T helper ( TH17) cells.
Original research paper: Cell 126, 1121 – 1133, (2006) |
 | Strange bedfellows
A new study shows that the Ras effector RALB can couple the activation of the immune system to tumor cell survival.
Original research paper: Cell 127, 157 – 170, (2006) |
 | A discriminating position
Purine-purine mismatches at position 16 of small interfering RNA (siRNA) strands provide the highest level of discrimination between genes that differ by a single nucleotide.
Original research papers: PLoS Genet. 2, 1307-1318, (2006); Nature Rev. Genet. 5, 355–365, (2006) |
 | Sweet dreams for sleepy flies
Increased social experience early in life causes flies to sleep more during the day; this effect may be mediated by signaling pathways that are involved in long-term memory.
Original research paper: Science 313, 1775 – 1781, (2006) |
 | The inside tag
An uncharged and cell-permeable coenzyme A (CoA) precursor is being used to covalently label proteins in living cells.
Original research paper: J. Am. Chem. Soc. 127, 11234 – 11235, (2005) |
