A study led by researchers at the Institute of Genetics and Cancer has uncovered the crucial role played by the protein TPR during oncogene-induced senescence. Abstract from paper Cells can respond to cancer-driving oncogenes by triggering an irreversible cell cycle arrest called senescence.Senescent cells activate a gene expression programme that leads to the secretion of inflammatory proteins that can affect how tumours grow. The team investigated what triggers this inflammatory gene expression programme and discovered an unexpected link between TPR - located at the pores used to transport material into and out of the nucleus - and chromatin re-organisation and loss of structural integrity at the edge of the nucleus, during these early stages of oncogene-induced senescence. This loss of structural integrity results in bits of the genome breaking off from the nucleus and ending up in the cytoplasm where it triggers the cellular machinery that normally senses viral infection. We show that this is the trigger for activation of the inflammatory state during the response to oncogenes. Whether TPR has a similar role for other triggers of senescence and in aging remains to be determined. Professor Wendy Bickmore Director of MRC Human Genetics Unit Link to paper in elife. Tags 2025 Publication date 07 Jan, 2025
