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.
 | NF-κB signaling: Bridging the noncanonical gap
Cellular inhibitors of apoptosis (cIAPs) ubiquitylate TRAF3 in a TRAF2-dependent manner, leading to NF-κB-inducing kinase (NIK) stabilization and the activation of the noncanonical NF-κB pathway.
Original research paper: Nature Immunology 9, 1364-1370 (2008) |
 | p53: Arginine methylation PRoMoTes cell-cycle arrest
Following DNA damage, PRMT5-stimulated arginine methylation of p53 elicits cell-cycle arrest in favor of apoptosis.
Original research paper: Nature Cell Biology 10, 1431-1439 (2008) |
 | Angiogenesis: VEGFR and PDGFR antagonism
Vascular endothelial growth factor receptor-2 (VEGF-R2) binds to and antagonizes platelet-derived growth factor receptor-β (PDGF-Rβ), which inhibits pericyte recruitment and limits neovascularization.
Original research paper: Nature 456, 809-813 (2008) |
 | Endocytosis: The importance of ART in trafficking
Two studies now report the identification of a family of arrestin-related proteins that target specific plasma membrane proteins for endocytic downregulation, by serving as adaptors for Rsp5, the Nedd4-like ubiquitin ligase in yeast.
Original research paper: EMBO Rep. 9, 1216–1221 (2008) |
 | Immunotherapy: Designer siRNA
A short interfering RNA (siRNA) has been designed that acts as a potent antitumor agent not only by silencing the expression of the anti-apoptotic gene Bcl2 (B-cell lymphoma 2) but also by triggering the innate immune receptor RIG-I (retinoic-acid-inducible gene I) to induce an antitumor immune response.
Original research paper: Nature Med. 14, 1256–1263 (2008) |
 | In brief: December 2008
Cell adhesion | DNA repair | Signalling | B cells | Apoptosis | Tumour biology | Synthetic biology | Learning and memory | Neurodengenerative disease | Analgesia | Metabolomics | Bacterial genetics |
 | Glioblastoma: Stop acting so immature
In humans, PTEN mutations are typically found in high-grade primary glioblastoma multiforme (GBM), whereas TP53 mutations are more common in secondary GBM; however, tumors in mice lacking both Pten and Trp53 in the CNS bear a striking resemblance to primary GBM in humans.
Original research paper: Nature 455, 1129–1133 (2008) |
 | Technology: Computing in a cell
A synthetic RNA device has been constructed that can integrate into and act on various molecular signals in a yeast system.
Original research paper: Science 322, 456–460 (2008) |
 | Apoptosis: New strategies to tip the BCL-2 balance
A peptide has been described that can convert BCL-2 from a protector into a potent killer, and a previously unknown activation site of the pro-apoptotic protein BAX has been identified.
Original research paper: Cancer Cell 14, 285–298 (2008) |
 | Chemical biology: No sunshine in a spotless mind?
Chemical-genetic manipulation of enzyme activity allows specific memory erasure in the mouse.
Original research paper: Neuron 60, 353–366 (2008) |
 | Innate immunity: Seeing mTOR in a new light
Rapamycin-mediated inhibition of mTOR in human phagocytes increases the production of pro-inflammatory cytokines and decreases the production of the anti-inflammatory cytokine IL-10.
Original research paper: Immunity 29, 565–577 (2008) |
 | Signalling: Making more of a mark
Notch 1 is required for Akt-dependent oncogenic transformation and melanocyte growth.
Original research paper: J. Clin. Invest. 118, 3660–3670 (2008) |
 | Gene networks: Network analysis gets dynamic
Expression analyses of the Saccharomyces cerevisiae metabolic network illuminate the timing of mRNA transcription and degradation.
Original research paper: Nature Biotechnol. 26, 1251–1259 (2008) |
 | Ion channels: Small conductance, big effects
Stress hormones activate ß-adrenoceptor G-protein-coupled receptors to enhance long-term potentiation (LTP), providing an explanation for why emotionally salient memories are better remembered than neutral ones.
Original research paper: J. Neurosci. 28, 10803–10813 (2008) |
 | Protein biochemistry:: Hotwiring protein regulation
An algorithm for identifying allosteric mechanisms — in which ligand binding at one protein site triggers functional changes at another remotely positioned site — allows researchers to assemble a functional multidomain protein.
Original research paper: Science 322, 438–442 (2008) |
 | Cell signalling: Range over strength
A data-driven signaling network model shows that the dynamic range of activation of a given signaling molecule might be a better predictor of functional responses than signal strength.
Original research paper: Cell 135, 343–354 (2008) |
 | Thymocyte development: New roles for TRPM7
The TRPM7 (transient receptor potential melastatin related 7) ion channel is essential for embryonic development and thymopoiesis, but not for Mg2+ homeostasis.
Original research paper: Science 322, 756–760 (2008) |
 | Stem cells: A new pathway for stem cell ageing and renewal
The transcriptional regulator high-mobility group A2 (HMGA2) promotes neural stem cell self-renewal by negatively regulating INK4A and ARF expression.
Original research paper: Cell 135, 227–239 (2008) |
 | Synapse formation: The missing link
The low-density lipoprotein receptor LRP4 binds to neuronal agrin and induces phosphorylation of MuSK to regulate postsynaptic clustering of acetylcholine receptors (AChRs) at neuromuscular junctions.
Original research paper: Cell 135, 334–342 (2008) |
 | G-protein-coupled receptors: A novel double act
The muscarinic acetylcholine receptor (mAChR) agonist McN-A-343 can bind to both the orthosteric and allosteric sites on the M2 mAChR to modulate the response to ligand.
Original research paper: J. Biol. Chem. 283, 29312–29321 (2008) |
