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.
Tumorigenesis: IKKα goes nuclear A new nuclear role has been described for IκB kinase alpha (IKKα) in the promotion of metastasis in response to proinflammatory signals. Original research paper: Nature446, 690-694 (2007)
Signaling crosstalk: A Ras and p53 pas de deux The synergistic effect of the activation of the small GTPase Ras and the loss of the tumor suppressor p53 in tumorigenesis is due in part to their coordinated effect on RhoA localization and activation, which consequently affects cancer cell motility, invasion and metastasis. Original research paper: Nature Structural & Molecular Biology14, 215-223 (2007)
Signal transduction: Erk gives feedback Researchers have used a new tool to dissect the divergent effects of neuronal and epidermal growth factor on the function of the Raf–Mek–Erk mitogen-activated protein kinase (MAPK) pathway. Original research paper: Nature Cell Biology9, 324-330 (2007)
Cancer genes: Selecting decision makers High throughput sequencing of a spectrum of cancers allows the identification of genes that induce and sustain cancer growth. Original research paper: Nature446, 153-158 (2007)
Scaffolds: Delineating signaling specificity The scaffold protein Dlgh1 couples T-cell receptor signaling to activation of the p38 serine/threonine kinase. Original research paper: Nature Immunology8, 154-161 (2007)
Notch mediates the sprouting of tip cells Notch signaling counteracts vascular endothelial growth factor (VEGF)-mediated angiogenesis, supporting a role for Notch signaling pathway proteins as possible anti-cancer therapy targets. Original research paper: Nature445, 776-780, (2007)
Dissecting the instabilities Cyclin E deregulation leads to genomic instability independently of cyclin-dependent kinase activity. Original research paper: Mol. Cell25, 127 – 139, (2007)
Chemoresistance: Priming resistance Three tyrosine kinases are able to phosphorylate and inhibit cyclin-dependent kinase inhibitor 1B (CDKN1B; also known as p27), giving rise to chemotherapy resistance and poor cancer prognosis. Original research paper: Cell128, 281 – 294, (2007)
Gene expression live on view Magnetic labeling of DNA probes complementary to c-fos mRNA enables researchers to track mRNA distribution and assess transcriptional activity in real time. Original research paper: J. Neurosci.27, 713 – 722, (2007)
Double death for cancer cells Blocking autophagy in addition to chemotherapy significantly increases the incidence of complete clinical remission in a mouse model of B-cell lymphoma. Original research paper: J. Clin. Invest.117, 326 – 336, (2007)
Making mice at high speed Laser-assisted injection of embryonic stem cells (ESCs) into 8-cell stage embryos yields mice that are fully ESC-derived. Original research paper: Nature Methods4, 196 - 197, (2007)
Reaching one's range Morphogens with different gradient ranges, such as Decapentaplegic (Dpp) and Wingless (Wg), have different mechanisms and kinetics of spreading through the epithelium. Original research paper: Science315, 521 – 525, (2007)
Floxed foxes The deletion of all three FOXO (forkhead box O) family transcription factors is necessary to induce a cancer-prone condition in mice. Original research paper: Cell128, 309 – 323, (2007)
Aneuploidy throws up a surprise There is now formal confirmation that not only can aneuploidy promote tumorigenesis, but that, in certain cellular contexts, it can also inhibit tumor formation. Original research paper: Cancer Cell11, 25 – 36, (2007)
Putting 2 and 2 together A tubulin gene mutation causes abnormal neuronal migration in mice, and this mutation is also present in humans with lissencephaly — a rare brain formation disorder. Original research paper: Cell128, 45 – 57, (2007)
Counting orexins An orexin receptor antagonist elicits sleepiness without cataplexy at single doses administered orally during the active period of the circadian cycle. Original research paper: Nature Med.13, 150 – 155, (2007)
Unraveling transcriptional networks Analysis of microarray data to decipher regulatory networks is facilitated by novel computer algorithms that explain the regulatory connections between a transcription factor and gene expression. Original research paper: PLoS Biol.5, e8 (2007)
1918 — a lesson from history? The ability of the 1918 virus to modulate host immune responses, including the expression of pro-inflammatory cytokines, could have contributed to its unprecedented lethality. Original research paper: Nature445, 319 – 323, (2007)
A signalling integration node The p53 tumor suppressor protein couples Ras signaling to TGFβ-mediated transcriptional activity to influence cellular differentiation and proliferation. Original research paper: Science315, 840 – 843, (2007)
Vitamin D3 promotes immune function in the skin Vitamin D3 induces expression of Toll-like receptor 2 and CD14 during wound healing. Original research paper: J. Clin. Invest.117, 803 - 811, (2007)
Collusion Knocking out the protein tyrosine phosphatase PTPN1 in mice that overexpress ERBB2 delays the onset of tumorigenesis, thus establishing PTPN1 as a potential target for anti-cancer therapies. Original research paper: Nature Genet.39, 338 - 346, (2007)
Transcription and translation get together Coupling transcription and translation via internal ribosome entry sites (IRES) in the insulin-like receptor gene (InR) allows Drosophila to rapidly adapt to changes in nutrient availability. Original research paper: Genes Dev.21, 175 – 183, (2007)
Pathways to treatment A mouse model of Parkinson's disease provides hope that therapies boosting the levels of endocannabinoids present at indirect pathway synapses may improve motor skills in human patients. Original research paper: Nature (8 Feb 2007)
Human mice Bacterial artificial chromosomes (BACs) allow large amounts of mouse DNA to be replaced with the corresponding human sequence, giving rise to a technological coup in the development of mouse models for human disease. Original research paper: Cell128, 197 – 209, (2007)
PTEN — a new guardian of the genome Three studies have provided insight into how ubiquitylation regulates phosphatase and tensin homologue (PTEN) stability and its nuclear localization, as well as the role of nuclear PTEN in chromosomal integrity. Original research paper: Cell128, 129 – 139, (2007)
Releasing control When neuroepithelials cells divide asymmetrically they reduce the size of the apical plasma membrane in part by releasing some of the membrane into the extracellular space. Original research paper: J. Cell Biol. (2007)
The SOX switch The transcription factor SOX13 may function as a negative regulator of cell division and inhibit the transition of αβ to γδ T cells. Original research paper: Science315, 230 – 233, (2007)
New switch to activate class B GPCRs A glucagon-like peptide 1 (GLP1) receptor agonist has been identified that stimulates glucose-dependent insulin release. Original research paper: Proc. Natl Acad. Sci. USA104, 937 – 942, (2007)
An iron-clad interaction Transferrin receptor 1 (TfR1) is the host cellular receptor for the four New World hemorrhagic fever arenaviruses — Junin, Machupo, Guanarito and Sabia. Original research paper: Nature (07 February 2007)
A smooth handover Studying the three-dimensional structure of an intermediate ubiquitin-activating complex has shed light on the mechanisms the govern the smooth handover of ubiquitin between enzymes. Original research paper: Nature445, 394 – 397, (2007)
Building bridges with NF-κB The discovery of a nuclear factor-κB inhibitor that modulates the NF-κB-mediated response to both inflammation and developmental stimuli bridges these two seemingly disparate NF-κB functions. Original research paper: Cell128, 369 – 381, (2007)
Therapy: Restoration Several reports show that restoring p53 expression in p53-null tumors promotes regression through the induction of apoptosis, senescence and immune response. Original research paper: Cell127, 1323 – 1334, (2006)
Window of opportunity Treatment of glioblastoma patients with a pan-vascular endothelial growth factor receptor (pan-VEGFR) inhibitor alleviated edema and caused a significant but transient decrease in tumor volume. Original research paper: Cancer Cell11, 83 – 95, (2007)
Central government versus local control Tissue-specific repression of the transcription factor BMAL1 illuminates the contribution of local versus systemic stimuli in regulating circadian patterns of gene expression. Original research paper: PLoS Biol.5, e34 – 556, (2007)
