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.
 | Tyrosine kinases: An ABL gatekeeper
Mutation of a threonine near the active site of tyrosine kinases leads to persistent kinase activation and drug resistance.
Original research paper: Nature Structural & Molecular Biology 15, 1109-1118 (2008) |
 | Glioblastoma: An atlas of signaling pathways
The Cancer Genome Atlas Research Network has generated a comprehensive data set of proteins and signaling pathways that are deregulated in glioblastoma, which can be used to explore the molecular mechanisms of tumorigenesis and inform the development of targeted therapies.
Original research paper: Nature 455, 1061-1068 (2008) |
 | Rapamycin: Interferon with TLR-mediated antiviral immunity
The PI(3)K–mTOR signaling pathway regulates Toll-like receptor-stimulated production of type I interferons in plasmacytoid dendritic cells.
Original research paper: Nature Immunology 9, 1157-1164 (2008) |
 | TGF-β signaling: A new route to p38 and JNK
TGF-β activates p38/JNK through TRAF6-mediated polyubiquitylation of TAK1.
Original research paper: Nature Cell Biology 10, 1199-1207 (2008) |
 | Colon cancer: A β-catenin–CDK8–E2F1 ménage à trois
CDK8 and E2F1 have antagonistic roles in β-catenin-mediated transcription.
Original research paper: Nature 455, 547-551 (2008) |
 | Membrane trafficking: Endurance of the weakest signal
Strongly activated STAT3 diffuses from the cytoplasm into the nucleus, whereas weakly activated STAT3 is shepherded to the nucleus by a microtubule-dependent process.
Original research paper: J. Cell Biol. 182, 855–863 (2008) |
 | Regulatory T cells: MicroRNAs maintain identity
MicroRNA-dependent regulation of gene expression has an important role in the maintenance of TReg-cell homeostasis and suppressive capacity.
Original research paper: J. Exp. Med. 205, 1983–1991 (2008) |
 | In brief: October 2008
Signal transduction | Vaccines | HIV | Natural killer T cells | Metastasis | Oncogenes | Signalling | Development | Molecular neuroscience | Addiction | Nuclear receptors | Muscular disorders | Proteomics | Bioinformatics |
 | Genetics: More than one way....
Unbiased, systematic approaches to cataloging the genetic alterations in cancer should lead to a comprehensive understanding of the changes that occur during tumor development and treatment.
Original research paper: Nature 455, 1061–1068 (2008) |
 | Transcriptomics: There's nothing abnormal about chimeric RNA
Trans-splicing of individual mRNAs resulting in the fusion of the first 3 exons of JAZF1 to the last 15 exons of JJAZ1 has been detected in endometrial cancers, but may also play a role in protecting normal endometrial cells from apoptosis.
Original research paper: Science 321, 1357–1361 (2008) |
 | Development: Dynein branches out
The motor protein dynein helps establish neuronal axonal and dendritic characteristics by controlling the localization of the cellular branching machinery.
Original research paper: Nature Cell Biol. 10, 1164–1171 (2008) |
 | Innate immunity: STING: adding to the antiviral arsenal
STING (stimulator of interferon (IFN) genes) is an ER adaptor protein that mediates host responses to pathogen-derived nucleic acids.
Original research paper: Nature 455, 674-678 (2008) |
 | Tumorigenesis: Taking the MYC
Expression of a dominant-negative MYC mutant known as Omomyc reduces lung tumor volume in mice without causing obvious side effects, suggesting that MYC inhibition might be an effective anticancer strategy.
Original research paper: Nature 455, 679-683 (2008) |
 | Epigenetics: Losing control
Age-related dysregulation of the chromatin-remodeling enzyme histone deacetylase 1 (HDAC1) contributes to age-induced loss of remyelination efficiency in mice.
Original research paper: Nature Neurosci. 11, 1024-1034 (2008) |
 | Autoimmune disease: Blocking the drivers
A protein kinase C (PKC) inhibitor AEB071 has potential as a novel treatment for psoriasis and other human diseases that are associated with aberrant T-cell activation.
Original research paper: J. Clin. Invest. 118, 3151-3159 (2008) |
 | Molecular libraries: A surrogate scaffold tested
Exogenous scaffold proteins that contain pre-B-cell surrogate light chains derived from individuals with immunity against the H5N1 influenza virus are capable of binding to the viral hemagglutinin antigen with high affinity.
Original research paper: Proc. Natl. Acad. Sci. USA 105, 10756-10761 (2008) |
 | Development: Brown fat: muscle undercover?
The transcriptional regulator PRDM16 mediates the bidirectional cell fate switch between muscle and brown fat.
Original research paper: Nature 454, 961-967 (2008) |
 | Autoimmunity: The threat within
3' repair exonuclease 1 (TREX1) prevents cell-intrinsic autoimmunity by recognizing and metabolizing retroviral, but not 'self' genetic material.
Original research paper: Cell 134, 587-598 (2008) |
 | Anticancer Drugs: Partnering to promote apoptosis
Combining novel agents that target apoptotic pathways with other approved cancer drugs can enhance tumor-cell apoptosis.
Original research paper: J. Clin. Invest. 118, 3109-3122 (2008) |
 | Immunotherapy: Cancer cells BiTE the dust
A novel strategy that uses bispecific antibodies to physically tether cytotoxic T cells to tumor cells has shown promise in a Phase I clinical trial of patients with relapsed B-cell non-Hodgkin's lymphoma.
Original research paper: Science 321, 974-977 (2008) |
 | Antibodypedia
The 'Antibodypedia' is a wiki-based web portal that allows users to share information about antibodies along with raw data from western blots, immunohistochemistry, protein array and immunofluorescence.
Original research paper: Mol. Cell Proteomics 7, 2028-2037 (2008) |
 | Cell division: Back and forth
The transcriptional repressor hairy and enhancer of split-1 (HES1) enables quiescent cells to resume proliferation following prolonged cell-cycle arrest.
Original research paper: Science 321, 1095-1100 (2008) |
 | T-cell activation: Variation is the spice of life
Phenotypic variability within a clonal T-cell population is achieved by stochastic expression of CD8 and the phosphatase SHP1 (SRC-homology-2-domain-containing protein tyrosine phosphatase 1).
Original research paper: Science 321, 1081-1084 (2008) |
 | Therapy: Combine and conquer
Choosing the best combination of therapies for patients with progressive or non-responsive forms of cancer is enhanced by understanding the PTEN-Akt-mTOR and MAPK signaling feedback loops that lead to the evasion of therapeutic responses in cancer.
Original research paper: J. Clin. Invest. 118, 3065-3074 (2008) |
 | Immunomodulators: Two for the price of one?
The novel immunosuppressant drug FTY720 (fingolimod) is a sphingosine-1-phosphate analog that can clear chronic viral infections in mice.
Original research paper: Nature 454, 894-898 (2008) |
 | Imaging and visualization: New twists on photoswitchable proteins
Fluorescent proteins with novel photoswitching properties allow multilabel imaging at a single detection wavelength and dual-color super-resolution microscopy.
Original research paper: Nat. Biotechnol. 26, 1035-1040 (2008) |
 | Post-translational modification: Picking apart polyubiquitin chains
Antibodies that discriminate between Lys-63-linked and Lys-48-linked ubiquitin chains have revealed that polyubiquitin editing might be a general mechanism for attenuating signaling.
Original research paper: Cell 134, 668-678 (2008) |
 | Inflammation: Dealing with excessive cell death
Macrophage-inducible C-type lectin (Mincle) recognizes an endogenous ligand that is released from dead cells, as well as triggering the production of cytokines and chemokines that attract neutrophils to damaged tissue.
Original research paper: Nature Immunol. 1179-1188 (2008) |
 | Metastasis: Micro silencing
Hypermethylation of microRNAs could lead to their deregulated expression, which has been implicated in the development of tumor metastases.
Original research paper: Proc. Natl Acad. Sci. USA 105, 13556-13561 (2008) |
 | Antipsychotics: Tuning muscarinic receptor signalling
The small-molecule modulator LY2033298 specifically potentiates acetylcholine binding to the M4 muscarinic acetylcholine receptor subtype and shows promising effects in preclinical models of schizophrenia.
Original research paper: Proc. Natl Acad. Sci. USA 105, 10978-10983 (2008) |
 | Phosphorylation and the cell cycle
Two groups used quantitative mass spectrometry to look at changes in protein phosphorylation across the cell cycle.
Original research paper: Proc. Natl. Acad. Sci. USA 105, 10762-10767 (2008) |
