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A Promoter that Acquired p53 Responsiveness During Primate Evolution¹

Institut für Virologie, Philipps-Universität Marburg, 35037 Marburg [A. C., M. D.], and Primate Genetics [H. Z.] and Reproductive Biology [A. E.], German Primate Center, 37077 Göttingen, Germany

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.

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