A promoter that acquired p53 responsiveness during primate evolution.
The tumor suppressor p53 activates the transcription of human PIG3 through direct interaction with a polymorphic microsatellite sequence, (TGYCC)(n). Here, the evolution of this p53-responsive element was recapitulated. Comparison between primate species revealed that the PIG3 promoter acquired this sequence element in its full length only in Hominoidea (apes and humans), whereas the number of TGYCC repeats is far lower in monkeys. Accordingly, only the PIG3 promoters from Hominoidea respond efficiently to p53, whereas those from monkeys respond poorly or not at all. In parallel, the PIG3 gene was strongly induced by p53 in human and chimpanzee cells but was unaffected by p53 in cells derived from a common marmoset monkey. Thus, a novel p53 target gene appeared as recently as during the evolution of primates. This suggests that mechanisms of tumor suppression are subject to ongoing evolution in humans and their closest relatives.
Contente
Ana
A
Institut für Virologie, Philipps-Universität Marburg, Germany.
Zischler
Hans
H
Einspanier
Almuth
A
Dobbelstein
Matthias
M
D000818:Animals; D001483:Base Sequence; D019143:Evolution, Molecular; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D018895:Microsatellite Repeats / Q000235:genetics; D008969:Molecular Sequence Data; D011323:Primates / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins; D014162:Transfection; D014407:Tumor Cells, Cultured
D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; C411296:TP53I3 protein, human