Elephant TP53-RETROGENE 9 induces transcription-independent apoptosis at the mitochondria

Aidan J. Preston, Aaron Rogers, Miranda Sharp, Gareth Mitchell, Cristhian Toruno, Brayden B. Barney, Lauren N. Donovan, Journey Bly, Ryan Kennington, Emily Payne, Anthony Iovino, Gabriela Furukawa, Rosann Robinson, Bahar Shamloo, Matthew Buccilli, Rachel Anders, Sarah Eckstein, Elizabeth A. Fedak, Tanner Wright, Carlo C. MaleyWendy K. Kiso, Dennis Schmitt, David Malkin, Joshua D. Schiffman, Lisa M. Abegglen

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Approximately 20 TP53 retrogenes exist in the African and Asian elephant genomes (Loxodonta Africana, Elephas Maximus) in addition to a conserved TP53 gene that encodes a full-length protein. Elephant TP53-RETROGENE 9 (TP53-R9) encodes a p53 protein (p53-R9) that is truncated in the middle of the canonical DNA binding domain. This C-terminally truncated p53 retrogene protein lacks the nuclear localization signals and oligomerization domain of its full-length counterpart. When expressed in human osteosarcoma cells (U2OS), p53-R9 binds to Tid1, the chaperone protein responsible for mitochondrial translocation of human p53 in response to cellular stress. Tid1 expression is required for p53-R9-induced apoptosis. At the mitochondria, p53-R9 binds to the pro-apoptotic BCL-2 family member Bax, which leads to caspase activation, cytochrome c release, and cell death. Our data show, for the first time, that expression of this truncated elephant p53 retrogene protein induces apoptosis in human cancer cells. Understanding the molecular mechanism by which the additional elephant TP53 retrogenes function may provide evolutionary insight that can be utilized for the development of therapeutics to treat human cancers.

Original languageEnglish (US)
Article number66
JournalCell Death Discovery
Issue number1
StatePublished - Dec 2023

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research


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