Research Highlights

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

February 2012

• Signalling: SRC and survival

  

  When deregulated, the tyrosine kinase SRC can cause havoc in cells in which it is overexpressed. Recent results from Margaret Frame, Simon Wilkinson, Emma Sandilands and colleagues have shown that, in cancer cells in which the SRC pathway is hyperactive, active SRC is subject to autophagy as a route to enable cancer cell survival.

  Original research paper Nature Reviews Cancer 12 80 - 81 doi:10.1038/nrc3208

• Cancer stem cells: TAZ takes centre stage

  

  Epithelial to mesenchymal transition (EMT) is a process in which cells lose epithelial-like characteristics, such as cell–cell adhesion and polarity, and acquire mesenchymal properties that include increased motility. Most carcinomas exhibit a partial EMT, which is thought to promote the formation of cell populations that are enriched in cancer stem cells (CSCs). Two groups have recently found that transcriptional co-activator with PDZ-binding motif (TAZ), which is a component of the Hippo signalling pathway, is a regulator of CSC-like properties in breast cancer and mesenchymal transition in malignant glioma.

  Original research paper Nature Reviews Cancer 12 82 - 83 doi:10.1038/nrc3210

• Ubiquitylation: DUBs' key to selectivity

  

  Some deubiquitylating enzymes (DUBs) are specific for distinct ubiquitin linkages, but the molecular basis for this is largely unknown. TRABID, a DUB belonging to the ovarian tumour (OTU) family, has previously been shown to hydrolyze atypical Lys29-linked ubiquitin chains more efficiently than other linkages. Komander and colleagues now reveal how a ubiquitin-binding domain (UBD) contributes to this specificity.

  Original research paper Nature Reviews Molecular Cell Biology 13 64 - 65 doi:10.1038/nrm3268

• Cell cycle: AMPK moonlights in mitosis

  

  AMP-activated protein kinase (AMPK) is well known for its ability to regulate cell metabolism, but emerging evidence suggests that it functions in additional cellular processes. Banko et al. have identified novel substrates of AMPKα2 (a catalytic subunit of AMPK) that have a role in mitosis, including protein phosphatase 1 regulatory subunit 12C (PPP1R12C).

  Original research paper Nature Reviews Molecular Cell Biology 13 64 - 65 doi:10.1038/nrm3275

• Synaptic plasticity: Ubiquitin activates synaptic plasticity

  

  Ubiquitylation of synaptic proteins and their subsequent degradation by the proteasome is thought to be a key mechanism for the regulation of synaptic plasticity. Ubiquitylation can also alter protein function by modifying interactions between proteins or by modulating protein activity; however, less is known about the roles of these non-proteolytic functions of ubiquitin in synaptic plasticity. Kandel and colleagues now show that ubiquitin-mediated modification of the activity of cytoplasmic polyadenylation element-binding protein 3 (CPEB3) regulates hippocampal-based long-term memory storage.

  Original research paper Nature Reviews Neuroscience 13 73 doi:10.1038/nrn3175