The Regulation of Exosome Secretion: a Novel Function of the p53 Protein

TLDR

p53 responds to stress signals by regulating transcription of many genes, some of which encode secreted proteins that may mediate communication between adjacent cells. The study aims to identify proteins secreted in a p53‑dependent manner after DNA damage. A proteomics approach was used to identify these proteins. The authors found that p53 activation increases secretion of proteins not transcriptionally regulated by p53 via exosomes, including TSAP6, which enhances exosome production, indicating that the p53 pathway regulates exosome release to communicate with neighboring and immune cells. Cancer Res 2006; 66(9): 4795‑801.

Abstract

Abstract The p53 protein responds to stress signals by regulating the transcription of a variety of genes. Some of these genes encode secreted proteins that may be involved in the communication between adjacent cells. In this study, a proteomics approach was employed to identify proteins secreted by cells in a p53-dependent manner after DNA damage. In addition to the known transcriptional targets of p53, a set of proteins encoded by genes that are not transcriptional targets of p53 were found to increase in the culture medium after p53 activation. These proteins exit the cell via small, secreted vesicles called exosomes and exosome production by cells was found to be regulated by the p53 response. A p53-regulated gene product, TSAP6, was shown to enhance exosome production in cells undergoing a p53 response to stress. Thus, the p53 pathway regulates the production of exosomes into the medium and these vesicles can communicate with adjacent cells and even cells of the immune system. (Cancer Res 2006; 66(9): 4795-801)