Research Highlights

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

November 2007

• Cell division: Fractal cycling

  

  Cell-cycle arrest in metaphase of meiosis II in an unfertilized animal egg is maintained by high cyclin-dependent kinase (CDK) activity. Following fertilization, a rapid transient increase in cytosolic Ca²⁺ mediates exit from meiosis, which is followed by numerous events that coordinate the formation of the diploid zygote. Two separate studies, led by Tim Hunt and Keita Ohsumi, have expanded our understanding of the initial signalling events downstream of the Ca²⁺ transient, which has important implications for the oscillatory regulation that coordinates exit from mitosis and meiosis (M-phase).The Ca²⁺/calmodulin-dependent kinase-II (CaMKII) is activated by the Ca²⁺ transient that follows fertilization of Xenopus laevis eggs, and CaMKII-dependent phosphorylation of Erp1 (an inhibitor of the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase) is a crucial downstream event that mediates its degradation. This allows APC/C to ubiquitylate and hence target cyclins — among other proteins — for degradation, which facilitates progression through and exit from M-phase by inhibiting CDK activity.

  Original research paper Nature Reviews Molecular Cell Biology 8 850 - 851 doi:10.1038/nrm2284

• Ageing: Falling p53 function

  

  The increased incidence of cancer with age is thought to occur because of the accumulation of mutations in cells with time, and many biological processes gradually decline in ageing organisms. Arnold Levine and colleagues asked whether the function of the tumour suppressor p53 could also decline with age and hence contribute to enhanced mutation frequency and tumorigenesis.

  Original research paper Nature Reviews Cancer 7 811 doi:10.1038/nrc2265

• Cancer genetics: Networks uncover new cancer susceptibility suspect

  

  Cancer susceptibility genes such as breast cancer 1 (BRCA1) do not function in isolation — they are parts of networks, and deciphering how these networks operate is an important step in understanding cancer progression. A new study has constructed a network for breast cancer susceptibility using various 'omic' data sets, and identified the hyaluronan-mediated motility receptor gene (HMMR) as a new susceptibility locus for the disease.

  Original research paper Nature Reviews Genetics 8 823 doi:10.1038/nrg2229

• Tumorigenesis: Size is everything

  

  How is tissue size regulated? This question has been occupying scientists for a long time, and although a few genetic regulators of organ size have been identified in organisms such as Drosophila melanogaster, the regulation of organ size in mammals is still perplexing. Do YAP and Yorkie hold the key?

  Original research paper Nature Reviews Cancer 7 815 doi:10.1038/nrc2258

• Tumorigenesis: A shocking enabler of tumour growth

  

  The conserved heat-shock response, mediated largely by the transcription factor heat-shock factor 1 (HSF1), allows cells to adapt to stress. Although this response is crucial to protect against some diseases of ageing, including ischaemia and neurodegenerative disorders, Susan Lindquist and colleagues now show that HSF1 has an opposite role in cancer, in which it promotes tumorigenesis.

  Original research paper Nature Reviews Cancer 7 817 doi:10.1038/nrc2262