A promoter that acquired p53 responsiveness during primate evolution

Area of Science:

• Evolutionary biology
• Molecular genetics
• Cancer research

Background:

• The tumor suppressor protein p53 regulates genes involved in cancer prevention.
• PIG3 is a known target gene of p53, activated through a specific DNA sequence.
• Understanding the evolutionary history of p53 target genes can reveal insights into cancer suppression mechanisms.

Purpose of the Study:

• To investigate the evolutionary origin and functional significance of the p53-responsive element in the human PIG3 promoter.
• To compare the p53-PIG3 interaction across different primate species.

Main Methods:

• Comparative sequence analysis of the PIG3 promoter across primate species.
• Functional assays in cell lines from different primate species to assess p53-mediated PIG3 induction.

Main Results:

• The full-length p53-responsive microsatellite sequence (TGYCC)(n) was acquired in the PIG3 promoter exclusively in Hominoidea (apes and humans).
• Primate species outside of Hominoidea, such as monkeys, possess fewer repeats and show significantly lower PIG3 promoter response to p53.
• p53 strongly induced PIG3 in human and chimpanzee cells, but not in common marmoset monkey cells.

Conclusions:

• The PIG3 gene emerged as a novel p53 target gene relatively recently in primate evolution, specifically within Hominoidea.
• The evolution of tumor suppression mechanisms, including p53 target genes, is an ongoing process in humans and closely related species.