Tuesday, November 9, 2010
Tumor Suppression Protein p53 and TRF2, Telomere-capping Complex Shelterin Exchange Positive Feedback During Telomere-damage Signalling and Cellular Senescence
Telomeres are capped at each end to protect them from degrading and from being recognized as damaged DNA. At the end of their lifespan, telomeres lose this protection and DNA-damage signaling pathways are triggered that activate p53. Harris and his team found that p53 controls TRF2 levels, through an intermediary component known as Siah-1. In this experiment, TRF2 was found to be repressed and Siah-1 was induced in normal human tissue cells when p53 was activated. The scientists also found that p53 affects DNA damage signaling from uncapped telomeres, as well as regulating the telomere-capping complex. This suggests that the p53-Siah-1-TRF2 pathway plays an integral part in orchestrating the DNA damage response of telomeres. Both p53 and telomeres have therapeutic significance in cancer. This discovery, therefore, provides not only a new mechanistic insight into p53- and telomere-based cancer therapeutics currently used or tested, but also the experimental basis for the development of new therapies, according to the scientists.
Nature Cell Biology via cancer.gov