Research Highlights

Short, accessible synopses of recent important articles concerning signalling pathways.

July 2007

• Tumour suppression: The power of arrest

  

  Cellular senescence is an irreversible cell-cycle arrest that can be triggered in response to several stimuli, including the shortening of telomeres. It has long been thought to represent a tumour suppression mechanism, but in vivo evidence has been lacking. Two studies that made use of sophisticated mouse cancer models now reveal the power of cellular senescence as a p53-mediated mechanism of tumour suppression.

  Original research paper Nature Reviews Molecular Cell Biology 8 514 - 515 doi:10.1038/nrm2200

• Cancer: Finding the right target

  

  Because of the frequent mutational activation of Ras in cancer, there is widespread interest in developing Ras inhibitors. However, because Ras has many downstream effectors that regulate complex signalling networks, there has been much debate regarding which effectors of Ras are most important during tumorigenesis. Gupta et al. now use mouse models of Ras-mediated tumorigenesis and validate the importance of the phosphatidylinositol 3-kinase (PI3K) pathway in Ras-induced tumorigenesis.

  Original research paper Nature Reviews Molecular Cell Biology 8 515 doi:10.1038/nrm2209

• DNA repair: The big and the small picture

  

  Systems biology approaches can reveal the broad range of players that are involved in a cellular process and, at the same time, open avenues of investigation around specific players, as is nicely illustrated by four reports in Science.

  Original research paper Nature Reviews Molecular Cell Biology 8 517 doi:10.1038/nrm2201

• MicroRNA: Another piece in the p53 puzzle

  

  The p53 network controls many pathways important for tumour suppression by regulating transcription. Three papers, by Moshe Oren and colleagues, Joshua Mendell and colleagues, and Gregory Hannon, Michele Cleary and colleagues, have shown that some of p53's functions may be mediated through transcriptional activation of microRNAs (miRNAs).

  Original research paper Nature Reviews Cancer 7 488 doi:10.1038/nrc2178

• Tumour suppressor: Surviving the tumour suppressor

  

  Autophagy — the breakdown of cellular proteins and organelles to sustain metabolism during starvation and metabolic stress — is thought to be a cell survival and, paradoxically, a cell death pathway. So why are genes that regulate autophagy selected against during tumorigenesis if loss of autophagy impairs tumour cell survival? Eileen White and colleagues might have found a mechanism that squares this circle.

  Original research paper Nature Reviews Cancer 7 490 - 491 doi:10.1038/nrc2179

• Cancer stem cells: Fishing for clues

  

  The molecular mechanisms that underlie the onset of rhabdo-myosarcoma (RMS) are still largely unknown. Ras mutations, for example, account for only a minority of embryonal RMS (ERMS), which is the most common subtype of paediatric RMS. Leonard Zon and colleagues have developed a powerful zebrafish model of Ras-induced ERMS, which allowed them to identify gene-expression signatures conserved in human ERMS and zebrafish ERMS (zERMS), and the cancer stem cell in zERMS.

  Original research paper Nature Reviews Cancer 7 490 - 491 doi:10.1038/nrc2181

• Regulatory T cells: Adding adenosine to the mix

  

  CD4⁺CD25⁺ regulatory T (T_Reg) cells have an important role in maintaining immunological tolerance. However, methods to precisely identify these cells and their mechanisms of suppression are still under investigation. Now, two studies identify cyclic AMP (cAMP) and members of the adenosine-synthesis pathway as key factors in the identification and function of T_Reg cells.

  Original research paper Nature Reviews Immunology 7 493 doi:10.1038/nri2122

• Neurotransmitter receptors: Directing traffic

  

  Trafficking of neurotransmitter receptors and ion channels contributes to the regulation of synaptic function, and is thought to have a key role in synaptic plasticity. Both phosphorylation and ubiquitylation have been shown to trigger trafficking of synaptic proteins. In a new study, Martin & Nishimune et al. reveal a role for another post-translational modification, sumoylation, in kainate receptor (KAR) trafficking.

  Original research paper Nature Reviews Neuroscience 8 492 - 493 doi:10.1038/nrn2172

• Innate immunity: Turning on TLR9

  

  A new study published in Blood identifies the nuclear protein high-mobility group box 1 protein (HMGB1) as an important modulator of Toll-like receptor 9 (TLR9) activation by CpG-containing DNA (CpG DNA).

  Original research paper Nature Reviews Immunology 7 496 doi:10.1038/nri2124

• Signaling rewired

  

  Synthetic signaling molecules can be designed to display complex gating properties and to reprogram signaling networks in cells.

  Original research paper Nature Methods 4 537 doi:10.1038/nmeth0707-537