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 architecture: Spir models actin in new ways
Spir belongs to a novel class of actin nucleation factors that constructs actin-based structures specifically required for polarization.
Original research paper: Nature 433, 382 – 388, (27 January 2005) |
 | Cell cycle:
Simply effective
Bub1, a kinase involved in the regulation of several cell cycle checkpoint proteins, directly inhibits the activity of the anaphase-promoting complex/cyclosome (APC/C).
Original research paper: Mol. Cell 16, 387 – 397, (2004) |
 | In brief: January 2005
Cell fate | Chromatin | Ageing | Lymphocyte migration | HIV | Macrophages | Genetics | Colon cancer | Tumour suppressors | Cell adhesion | RNA silencing | Cell biology of the neuron | Stem cells | Cardiovascular disease | Anticancer drugs |
 | Transcription:
Nuclear actin muscles in
In addition to being implicated in RNA polymerase (Pol) II transcription, it has been shown that actin is also required for Pol I and Pol III transcription.
Original research paper: Nature Cell Biol. 6, 1165 – 1172, (2004) |
 | Mast cells:
Tempering toxicity
Mast cells have a new biological function; they can limit the toxicity and pathology associated with endothelin-1 (ET-1).
Original research paper: Nature 432, 512 – 516, (2004) |
 | Infectious disease:
West Nile virus makes an entrance
Recognition of West Nile virus (WNV) by Toll-like receptor 3 (TLR3) is the main factor that allows this virus to cross the blood–brain barrier and cause lethal encephalitis.
Original research paper: Nature Med. 10, 1366 – 1373, (2004) |
 | Apoptosis:
Checking in cell death
The cell cycle checkpoint kinases CHK1 and CHK2 activate the p73-mediated apoptosis pathway in response to DNA damage.
Original research paper: Genes Dev. 18, 3041 – 3054, (2004) |
 | Development:
Occupying the middle ground
Axin-1 regulates cell fate determination at the ventral midline by inhibiting Wnt/β-catenin signaling.
Original research paper: Development 131, 5923 – 5933, (2004) |
 | Screening:
Single cell screens
An automated microscopy method has been developed that can provide quantitative data relating to changes in phenotype of a single cell in response to different drugs.
Original research paper: Science 306, 1194 – 1198, (2004) |
 | New fluorescent protein includes handy on-off switch
A GFP-like protein with sensitive and reversible on–off switching capabilities represents the first of a new generation of specialized fluorescent tools for studying protein movement and trafficking inside cells.
Original research paper: Science 306, 1370 – 1373, (2004) |
 | Pokemon in tumorigenesis: An essential and harmful player
The transcriptional repressor Pokemon directly inhibits expression of the tumor suppressor gene ARF and plays a critical role in oncogenesis.
Original research paper: Nature 433, 278 – 285, (20 January 2005) |
 | Signalling:
The stretch effect
Forces on the extracellular matrix are transduced into intracellular signals through the small GTPase Rap1.
Original research paper: Dev. Cell 7, 709 – 718, (2004) |
 | Immune regulation:
IL-12 helps keep apoptosis quiet
Interleukin-12 expression in response to apoptotic cells can also be regulated by a new mechanism involving the novel zinc-finger nuclear factor GC-BP.
Original research paper: Immunity 21, 643 – 653, (2004) |
 | Lymphoma:
Ups and downs
The transcriptional repressor BCL6 suppresses the expression of p53 to block DNA-damage-induced apoptosis in developing B cells.
Original research paper: Nature 432, 635 – 639, (2004) |
 | Tumour suppressors:
A new SNP
An individual's susceptibility to cancer is influenced by naturally occurring polymorphisms in the components of the TP53/MDM2 tumor suppressor pathway.
Original research paper: Cell 119, 591 – 602, (2004) |
 | Behavioural genetics:
Beyond the body clock
New research reveals novel roles for genetic components involved in Drosophila melanogaster circadian rhythms, indicating that these genes have diverse biological functions.
Original research paper: Proc. Natl Acad. Sci. USA 101, 16058 – 16063, (2004) |
 | Pain:
The GluRA, B, C of pain
AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors, which are vital mediators of hippocampal plasticity, are also important modulators of inflammatory pain and of synaptic plasticity in the spinal nociceptive system.
Original research paper: Neuron 44, 637 – 650, (2004) |
 | Antiviral drugs:
Blocking the route to infection
A promising approach to improve the pharmacological properties of a natural protein that blocks HIV entry could also be applicable to other therapeutic proteins.
Original research paper: Proc. Natl Acad. Sci. USA 101, 16460 – 16465, (2004) |
 | Multidimensional cell profiling
High-throughput profiling of cellular markers by automated microscopy adds a powerful new method for probing cellular function.
Original research paper: Science 306, 1194 – 1198, (2004) |
 | Wnt signaling: Dishevelled dendrites
Wnt signaling through Dishevelled regulates neuronal dendrite development by a non-canonical mechanism that involves Rac and JNK.
Original research paper: Nature Neuroscience 8, 34 – 42, (2005) |
 | Technique:
Monitoring modification
Bioluminescence resonance energy transfer (BRET) is a new technique that can be used to detect in situ changes in protein ubiquitylation.
Original research paper: Nature Meth. 1, 203 – 208, (2004) |
 | Signalling:
Fill in the blanks...
Wnt signals through protein kinase A and cyclic-AMP-response-element-binding protein (CREB) to mediate induction of the myogenic determinants Pax3, MyoD and Myf5.
Original research paper: Nature (28 Nov 2004) |
 | Immune regulation:
BTLA finds its true partner
B- and T-lymphocyte attenuator (BTLA) does not interact with B7X, but instead interacts with herpesvirus-entry mediator (HVEM) to initiate signaling pathways that impair antigen-induced T-cell proliferation.
Original research paper: Nature Immunol. 6, 90 – 98, (2005) |
 | Autoimmunity:
Spot the difference
The affinity of the self-reactive T-cell receptor (TCR) for the foreign antigen is an important factor in regulating the initiation of autoimmunity.
Original research paper: Nature Med. 10, 1234 – 1239, (2004) |
 | Genetic profiling:
Of mice and men
A mouse model of Kras-generated lung cancer, which appears histologically similar to the human disease, has been used to identify a KRAS mutation gene signature in human cancers.
Original research paper: Nature Genet. 37, 48 – 55, (2005) |
 | Ion Channels:
Sensing the pressure
Phospholipids play an important role in the mechanical gating process through which the ion channel TREK-1 converts external mechanical forces into electrical and chemical signals in the cell.
Original research paper: EMBO J. 24, 44 – 53, (2004) |
 | Cardiovascular disease:
Oestrogen activates COX2 pathway
Female mice are protected from hardening of the arteries as a result of estrogen activation of the cyclooxygenase (COX)-2 enzyme, which causes an increase in the amount of the atheroprotective molecule prostacyclin, PGI2.
Original research paper: Science Express 2, 635 – 645, (2004 November 18) |
 | When chemistry meets biology, proteases prosper
Researchers from two separate institutes have jointly developed high-throughput assays to characterize proteases and their substrates.
Original research paper: Chem. Biol. 11, 1361 – 1372, (2004) |
 | Bacterial physiology: The dynamic ParM engine
New research shows that ParM, a bacterial structural homolog of actin that segregates plasmids prior to cell division, assembles into a dynamic polymerization engine.
Original research paper: Science 306, 1021 – 1025, (2004) |
 | Integrin signaling: A sticky situation
Epidermal growth factor receptor (EGFR) signaling is attenuated through the α1β1 integrin-mediated activation of the protein tyrosine phosphatase TCPTP.
Original research paper: Nature Cell Biology 7, 78 – 85, (2005) |
 | Cytoskeleton:
Keeping dynamic
A new haloacid dehydrogenase (HAD)-type phosphatase named chronophin (CIN) has been shown to dephosphorylate cofilin.
Original research paper: Nature Cell Biol. 7, 21 – 29, (2004) |
 | Cell cycle:
What goes around...
A new study provides insight into the effects that different components and regulators of the anaphase-promoting complex/cyclosome (APC/C) have on the degradation of cyclin A.
Original research paper: Nature 432, 588 – 595, (2004) |
 | Natural killer T cells:
New lipid ligand nourishes NKT-cell responses
A lysosomal glycosphingolipid — isoglobotrihexosylceramide (iGb3) — stimulates both human Vα24+ and mouse Vα14+ NKT cells.
Original research paper: Science 306, 1786 – 1789, (2004) |
 | Infectious diseases:
Forcing phagosomes to mature
The pathogen-mediated block in phagosomal maturation can be overcome through the induction of autophagy and the antimycobacterial effects of interferon-γ (IFN-γ) can be explained by its ability to stimulate this process.
Original research paper: Cell 119, 753 – 766, (2004) |
 | Metastasis:
One step closer
ERBB2 signaling increases the expression of a chemokine receptor whose ligand is highly expressed in tissues where metastases of breast cancer commonly develop.
Original research paper: Cancer Cell 6, 459 – 469, (2004) |
 | Functional genomics:
A comparative success
Research on the sea squirt shows that intraspecies sequence comparisons can be effective for identifying functional sequences — and that other organisms, including humans, might also benefit from the same strategy.
Original research paper: Genome Res. 14, 2406 – 2411, (2004) |
 | Infectious diseases:
Gaining entry to the CNS
Serotonin (5-hydroxytryptamine or 5-HT) receptor antagonists could provide a new therapeutic approach to treating leukoencephalopathy (PML) caused by the human JC polyomavirus (JCV).
Original research paper: Science 306, 1380 – 1383, (2004) |
 | Cardiovascular disease:
In keeping with tradition
Berberine — an alkaloid used in traditional Chinese medicine (TCM) — might be able to lower elevated levels of LDL ('bad') cholesterol in the blood, a major risk factor for heart disease.
Original research paper: Nature Med. 10, 1344 – 1351, (2004) |
 | A plan for when the ChIPs are down
A new microarray-based strategy offers a tool for the rapid and sensitive identification of binding sites throughout the genome for virtually any transcription factor.
Original research paper: Nat. Genet. 36, 1331 – 1339, (2004) |
 | Virology: Of mice and myxoma
The myxoma virus species barrier seems to be mediated by a host-cell signaling cascade — the extracellular signal-regulated kinase (Erk)1/2–interferon–STAT1 signaling pathway.
Original research paper: Nature Immunol. 5, 1266 – 1274, (2004) |
