The regulation of exosome secretion: a novel function of the p53 protein.
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.
Yu
Xin
X
Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey, USA.
Harris
Sandra L
SL
Levine
Arnold J
AJ
D000483:Alleles; D000818:Animals; D017209:Apoptosis / Q000502:physiology / Q000528:radiation effects; D014408:Biomarkers, Tumor / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D021984:Cyclophilin A / Q000378:metabolism; D022162:Cytoplasmic Vesicles / Q000378:metabolism* / Q000528:radiation effects; D004249:DNA Damage / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D010088:Oxidoreductases; D020648:Peptide Elongation Factor 1 / Q000378:metabolism; D010735:Phosphoglycerate Kinase / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012636:Secretory Rate / Q000528:radiation effects; D015843:Serpins / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D018841:HSP90 Heat-Shock Proteins; C493165:HSP90AB1 protein, human; D015513:Oncogene Proteins; D020648:Peptide Elongation Factor 1; D012333:RNA, Messenger; C085344:SERPIN-B5; D015843:Serpins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases; C486677:STEAP3 protein, human; D010735:Phosphoglycerate Kinase; C095157:ENO1 protein, human; D010751:Phosphopyruvate Hydratase; D021984:Cyclophilin A