Research Highlights

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

January 2007

• Arming the front line with TLR9

  

  Differential signalling from Toll-like receptor 9 (TLR9) on the apical and basolateral surfaces of intestinal epithelial cells (IECs) might provide one explanation for the normal immune tolerance to commensal bacteria in the gut, according to a study in Nature Cell Biology. IECs are highly polarized structures as a result of the markedly different environments that they interact with at the apical surface (the microflora of the intestinal lumen) and the basolateral surface (the lamina propria). Lee et al. investigated how such polarity affects the immune response to TLR ligands.

  Original research paper Nature Reviews Immunology 7 2 doi:10.1038/nri2006

• Oncogenic signalling: Mysteries of addiction

  

  Although several mutations and chromosomal aberrations typically contribute to the transformation of a cell, the inactivation of a single oncoprotein is sometimes enough to cause rapid apoptosis — it is as though the cancer cell has become dependent on a single oncogenic pathway that is not required in its noncancerous counterpart. Although such 'oncogene addiction' is important (and useful) for the development of targeted therapies, the underlying mechanism is not clear. Now, Jeffrey Settleman and colleagues propose a new mechanism to explain the phenomenon, which they feel is more accurately described as 'oncogenic shock'.

  Original research paper Nature Reviews Cancer 7 4 doi:10.1038/nrc2058

• A rapid-response stress switch

  

  The protein p53 exerts a pivotal role in controlling the cell cycle, apoptosis and DNA repair in response to various forms of genotoxic stress. The rapid activation of p53 following genotoxic stress is ensured through complex regulation that occurs mainly at the post-translational level. Huang and colleagues now add an extra factor to the regulation of p53 by showing that the lysine methyltransferase SMYD2 methylates p53.

  Original research paper Nature Reviews Molecular Cell Biology 8 5 doi:10.1038/nrm2093

• Which signal to respond to?

  

  Lymphocytes can receive multiple external signals at distinct sites on the cell surface during an immune response. But what determines which of the signals the lymphocyte responds to? Russell and colleagues propose a model by which the generation of alternative axes of polarization by a competing signal might determine the responsiveness of the cell to a subsequent distal signal.

  Original research paper Nature Reviews Immunology 7 6 - 7 doi:10.1038/nri2007

• Sharing the signalling components

  

  During mitosis, some cellular contents can be distributed randomly, whereas others must be distributed evenly between daughter cells. For example, components of the transforming growth factor- (TGF) pathway must be distributed evenly for viable development; the TGF pathway makes sense of the decapentaplegic (Dpp) morphogen gradient in Drosophila melanogaster wings to generate positional gene expression. In Science, Bökel et al. show that the endosomal protein Sara recruits thickveins (Tkv), the Dpp receptor, to a subset of endosomes that are distributed evenly in mitosis.

  Original research paper Nature Reviews Molecular Cell Biology 8 6 - 7 doi:10.1038/nrm2092

• Inhibiting the inhibitors

  

  The BCL2 protein family — a group of proteins that regulate cell death — can affect the sensitivity of tumour cells to chemotherapeutic agents. Because of this, several drugs have been developed that modulate their activity. Two papers published in Cancer Cell investigate the function of one of these drugs, ABT-737.

  Original research paper Nature Reviews Drug Discovery 6 25 doi:10.1038/nrd2239