Research Highlights

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

May 2009

• Cell cycle: Akt Skps through

  

  Cell cycle progression is regulated in part by the ubiquitylation and degradation of the cyclin-dependent-kinase inhibitor p27. SKP2 (S-phase kinase-associated protein 2) is a substrate-recognizing subunit of the SCF (SKP1 –CUL1–F-box) E3 ubiquitin ligase that ubiquitylates p27. Indeed, overexpression of SKP2 induces cell cycle entry, and cytoplasmic mislocalization of SKP2 has been detected in human cancers. The regulation of SKP2 localization and its incorporation into the SCF complex remains an area of active investigation. Two complementary studies in Nature Cell Biology now show that Akt-mediated phosphorylation of SKP2 promotes its accumulation in the cytoplasm and increases SCF complex formation, resulting in p27 ubiquitylation and degradation.

  Original research paper Nature Reviews Cancer 9 316 - 317 doi:10.1038/nrc2649

• Innate immunity: Targeting the messenger

  

  Shizuo Akira and colleagues have identified ZC3H12A as a Toll-like receptor (TLR)-inducible RNase that degrades specific cytokine mRNAs downstream of TLR signalling. Their results suggest that the regulation of mRNA stability might be as important as the control of transcription in regulating innate immune responses.

  Original research paper Nature Reviews Immunology 9 308 - 309 doi:10.1038/nri2552

• Autophagy: Breaking and exiting

  

  How cells switch from a proliferative state to a senescent state in response to cellular stress is not fully understood. Young et al. now suggest an intriguing new role for autophagy — a process that involves the lysosomal breakdown of cytoplasmic components — in the establishment of senescence.

  Original research paper Nature Reviews Molecular Cell Biology 10 302 - 303 doi:10.1038/nrm2671

• Neurogenesis: Assisted birth with DISC1

  

  Mutations in the gene disrupted in schizophrenia 1 (DISC1) have been associated with increased risk for schizophrenia as well as other mental disorders, including bipolar disorder and major depression. DISC1 is known to regulate diverse processes in postmitotic neurons during development, such as maturation and migration, but Tsai and colleagues now show that it also regulates the proliferation of both embryonic and adult neuronal progenitor cells by modulating glycogen synthase kinase 3β (GSK3β)–β-catenin signalling.

  Original research paper Nature Reviews Neuroscience 10 314 doi:10.1038/nrn2640

• T cell activation: Fine-tuning the immunological synapse

  

  Activation of T cells by antigen-presenting cells (APCs) requires the formation of a specific and long-lasting interface between the two cells, known as the immunological synapse. A recent study by Michael Dustin and colleagues shows that the actin-based motor protein myosin IIA has a central role in the formation and persistence of the immunological synapse and in signalling downstream of the T cell receptor (TCR).

  Original research paper Nature Reviews Immunology 9 306 - 307 doi:10.1038/nri2557