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.
 | Myocardial infarction: G-CSF rescues heart failure
Granulocyte colony-stimulating factor (G-CSF) activates the Jak/Stat pathway in cardiomyocytes to promote their suvival after myocardial infarction.
Original research paper: Nature Medicine 11, 305 – 311, (March 2005) |
 | Autophagy:
Survival factor
Even in the presence of excess nutrients, apoptosis-deficient cells that are deprived of growth factors undergo macroautophagy.
Original research paper: Cell 120, 237 – 248, (2005) |
 | In brief: March 2005
Autoimmunity | Regulatory T cells | Macrophages | Structure | Therapeutics | Viral oncogenesis | Tumour progression | Genetics | Plant technology | Epigenetics | Technology | Neurodegenerative disease | Lead discovery | DNA Cloning and Amplification | Cheminformatics | Microarrays | Virology |
 | Nuclear organization:
An organized exit
The recent characterization of the composition and assembly of senescence-associated heterochromatin foci (SAHF) has shed new light on the relationship between chromatin structure and senescence.
Original research paper: Dev. Cell 8, 19 – 30, (2005) |
 | Structure:
Do crystals reveal the secrets of HLA-B27?
The recently solved crystal structures of HLA-B27 in complex with three immunodominant viral peptides may help explain the association of this MHC class I allele with long-term non-progression to AIDS.
Original research paper: Eur. J. Immunol. 35, 341 – 351, (2005) |
 | Autoimmunity:
Raising the bar against lupus
Increasing the expression of FcγRIIB can be used to restore tolerance in a mouse model of the autoimmune disease systemic lupus erythematosus (SLE).
Original research paper: Nature Immunol. 6, 99 – 106, (2005) |
 | Epigenetics:
A silenced suppressor
A mouse model for acute leukaemic transformation has been used to measure the changes in CpG methylation that occur during the progression of leukaemia.
Original research paper: Nature Genet. 6, 95 – 108, (2005) |
 | Cell biology of the neuron:
The making of polarity
Glycogen synthase kinase 3β (GSK3β) may be a key factor in the translation of extracellular cues into cytoskeletal changes, thus shaping neuronal axons.
Original research paper: Cell 120, 123 – 135, (2005) |
 | Antiviral drugs:
A step ahead of drug resistance
The host-cell factor human deoxyhypusine synthase (DHS) provides a promising new target for the development of antiretroviral therapies to treat HIV-1.
Original research paper: J. Clin. Invest. 115, 76 – 85, (2005) |
 | Problem solved?
A recent study suggests that the Protein Data Bank (PDB) may — with the right computational tools — contain enough information to develop structure solutions for any single-domain protein.
Original research paper: Proc. Natl. Acad. Sci. USA 102, 1029 – 1034, (2005) |
 | BacterIal physiology:
Competitive signalling
A new study shows that N-acylhomoserine lactones (AHLs) — the quorum-sensing molecules that Gram-negative bacteria use to coordinate cell-density-dependent processes — can also function as antimicrobials.
Original research paper: Proc. Natl Acad. Sci. USA 102, 309 – 314, (2005) |
 | TNF signaling: A tyrosine phosphatase keeps the balance
T-cell protein tyrosine phosphatase is a negative regulator of Src-family tyrosine kinases in the induction of tumor-necrosis factor-dependent MAPK signaling.
Original research paper: Nature Immunology 6, 253 – 260, (March 2005) |
 | Signal transduction: A stabilizing modification
Acetylation of STAT3 is necessary for its stable dimerization and for its function as an activator of transcription.
Original research paper: Science 307, 269 – 273, (2005) |
 | Viral immunity: New mechanism for APOBEC3G?
The previously assumed absolute correlation between the cytidine-deaminase activity and antiretroviral function of APOBEC3G has now been called into question.
Original research paper: Curr. Biol. 15, 166 – 170, (2005) |
 | Mucosal immunology: DC networks access all areas
A new network of myeloid-derived CX3C-chemokine receptor 1 (CX3CR1)+ dendritic cells (DCs) in the lamina propria has now been described that can also directly sample luminal antigens.
Original research paper: Science 307, 254 – 258, (2005) |
 | Tumorigenesis: Growing through GEFs
The guanine nucleotide exchange factor (GEF) Vav1 also regulates an oncogenic pathway that promotes pancreatic cancer and could thus provide a new target for therapy.
Original research paper: Cancer Cell 7, 39 – 49, (2005) |
 | Gliogenesis: Oligodendrogenesis on a higher plane
The ventral neuroepithelium of the developing spinal cord might not be supplying the full complement of oligodendrocytes, but a more dorsal domain could be responsible for a second phase of oligodendrogenesis.
Original research paper: Neuron 45, 41 – 53, (2005) |
 | Cell fate: Striking the right balance
New light has been shed on the molecular mechanisms that control the fate of progenitor cells in the pMN progenitor domain of the embryonic ventral spinal cord.
Original research paper: Genes Dev. 19, 282 – 294, (2005) |
 | Drug resistance: Passing on protection
It now seems that drug-resistant cells can physically pass P-glycoprotein (P-gp) – a protein well established as a cause of multidrug resistance in cancer cells – on to drug-sensitive cells, enabling the recipient cells to survive potentially toxic drug concentrations.
Original research paper: Proc. Natl Acad. Sci. USA 102, 1933 – 1938, (2005) |
 | Mammalian cells put on a display
Using a chemokine receptor, researchers have generated a new system to display random peptide libraries on the surface of mammalian cells.
Original research paper: J. Biol. Chem. (18 January 2005) |
 | Bacterial pathogenesis: Coiled coils in type III secretion
A new report now describes the high-resolution structure of the Type III secretion system (TTSS) filament protein of enteropathogenic Escherichia coli (EPEC), EspA, in complex with its secretion chaperone, CesA.
Original research paper: Nature Struct. Mol. Biol. 12, 75 – 81, (2005) |
 | Immunity: IRF-5 fights its way into the TLR cascade
The transcription factor IRF-5 is a downstream regulator of the Toll-like receptor - MyD88 adaptor signaling pathway, which mediates the induction of proinflammatory cytokine genes in innate and adaptive immunity.
Original research paper: Nature 434, 243 – 249, (10 March 2005) |
 | Membrane trafficking:
Actin' out of control
The kinase Prk1 shuts off Arp2/3-mediated actin polymerization during endocytosis by directly phosphorylating and inactivating Pan1.
Original research paper: Nature Cell Biol. 7, 246 – 254, (2005) |
 | RNA interference:
Nuts and bolts
A new member of the polymerase-β nucleotidyltransferase superfamily – the Caenorhabditis elegans protein RDE-3 – may have a role in the RNAi pathway.
Original research paper: Curr. Biol. 15, 378 – 383, (2005) |
 | T cells:
PIM kinases to the rescue
Cytokine-induced PIM kinases promote T-cell survival in the presence of the immunosuppressive drug rapamycin.
Original research paper: J. Exp. Med. 201, 259 – 266, (2005) |
 | Therapeutics: Susceptibility or resistance?
Lung adenocarcinomas harboring KRAS mutations are resistant to the epidermal growth factor receptor inhibitory drugs gefitinib and erlotinib.
Original research paper: PLoS Med. 2, 57 – 61, (2005) |
 | Gene expression:
Transcriptional silencing: the third way
A new model for transcriptional silencing has been proposed, in which silencing occurs by preventing the formation of stable pre-initiation complexes at silenced promoters.
Original research paper: Cell 120, 37 – 48, (2005) |
 | Synaptic physiology: Neuroligin: the synaptic multitasker
The postsynaptic adhesion molecule neuroligin 1, in complex with its axonal receptor, β-neurexin, is involved in postsynaptic differentiation and may have an important role in maintaining the functional balance of excitatory and inhibitory synapses.
Original research paper: Science 307, 1324 – 1328, (2005) |
 | Cardiovascular disease:
Viagra for broken hearts?
According to a new study, the phosphodiesterase 5 (PDE5) inhibitor sildenafil citrate (Viagra) also prevents and reverses cardiac hypertrophy (enlarging of the heart).
Original research paper: Nature Med. 21, 214 – 222, (2005) |
 | A 'flaky' but useful fluorophore
A new fluorescent compound, with substantial advantages over previous fluorophores, promises to make the detection of small changes in protein conformation in living cells easier.
Original research paper: Proc. Natl. Acad. Sci. USA 102, 965 – 970, (2005) |
 | Virology: The missing link...
A host protein – the mannose 6-phosphate receptor (MPR) – might be a key molecule implicated in the mechanism of airborne virion infections.
Original research paper: Cell 119, 915 – 926, (2004) |
 | Tumor cell invasion: Not just a ROCKy ride
Cdc42-MRCK and Rho-ROCK signaling cooperate to control actomyosin contractility during elongated cell invasion.
Original research paper: Nature Cell Biology 7, 255 – 261, ( 2005) |
 | Systems biology:
The dynamics of the cycle
Analysis of protein complex dynamics during the yeast cell cycle has yielded a time-dependent interaction network that places 300 proteins in a temporal cell-cycle context.
Original research paper: Science 307, 724 – 727, (2005) |
 | Protein Translocation:
In or out?
Recent work on the sequence requirements of protein transmembrane helices has brought us closer to predicting the membrane-insertion efficiency of natural polypeptide segments.
Original research paper: Nature 433, 377 – 381, (2005) |
 | Cell migration:
AOC3 opens doors for leukocytes
The ectoenzyme amine oxidase copper-containing 3 (AOC3) has a new role in the regulation of leukocyte migration in vivo.
Original research paper: Immunity 22, 105 – 115, (2005) |
 | Inflammation:
Well connected
Chronic inflammation leading to an increase in macrophage migration inhibitory factor (MIF) expression antagonizes retinoblastoma (RB)-mediated repression of E2F-responsive genes and results in enhanced proliferation and tumorigenesis.
Original research paper: Mol. Cell 17, 225 – 236, (2005) |
 | RNA world:
The wide reach of microRNAs
Recent studies of animal miRNAs reveal a new mode of action for these molecules, and indicate that they might have a far wider regulatory role than was previously appreciated.
Original research paper: Nature 120, 15 – 20, (30 January 2005) |
 | Cell Biology of the neuron:
Motoring activity
Myosin VI might be the missing link between F-actin and neurotransmitter receptors, and could be crucial for synaptic vesicle endocytosis in neurons.
Original research paper: J. Cell Biol. 168, 329 – 338, (2005) |
 | Lead discovery:
Small is beautiful
The use of a novel fragment-based approach to drug screening has led to the discovery of a new family of potent and selective inhibitors of the enzyme phosphodiesterase 4 (PDE4), a therapeutic target for a range of inflammatory disorders.
Original research paper: Nature Biotechnol. 23, 201 – 207, (2005) |
 | Longer is better
The efficiency of RNA interference can be vastly improved by using longer RNA oligonucleotides, 27- to 29-mers instead of the conventional 21-mers.
Original research paper: Nat. Biotechnol. 23, 222 – 226, (2005) |
 | Plant pathogens: Signalling complexities for Pseudomonas
The virulence factor phytotoxin coronatine (COR) is required for Pseudomonas syringae's new-found ability to induce systemic-induced susceptibility (SIS) to subsequent infection.
Original research paper: Proc. Natl Acad. Sci. USA 102, 1791 – 1796, (2005) |
