@article{29960f8716ec4e3d89a335c4cf232c81,
title = "Elephant TP53-RETROGENE 9 induces transcription-independent apoptosis at the mitochondria",
abstract = "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.",
author = "Preston, {Aidan J.} and Aaron Rogers and Miranda Sharp and Gareth Mitchell and Cristhian Toruno and Barney, {Brayden B.} and Donovan, {Lauren N.} and Journey Bly and Ryan Kennington and Emily Payne and Anthony Iovino and Gabriela Furukawa and Rosann Robinson and Bahar Shamloo and Matthew Buccilli and Rachel Anders and Sarah Eckstein and Fedak, {Elizabeth A.} and Tanner Wright and Maley, {Carlo C.} and Kiso, {Wendy K.} and Dennis Schmitt and David Malkin and Schiffman, {Joshua D.} and Abegglen, {Lisa M.}",
note = "Funding Information: This research is supported through the EP53 Research Program and its generous funding provided to Huntsman Cancer Institute by the State of Utah. JDS is supported by Hyundai Hope on Wheels, Soccer for Hope Foundation, Li-Fraumeni Syndrome Association, and Kneaders Hope Fights Childhood Cancer. JDS was previously supported by the Edward B. Clark, MD Endowed Chair in Pediatric Research and currently by the Helen Clise Presidential Endowed Chair in Li-Fraumeni Syndrome Research. LMA and this research is supported by Primary Children{\textquoteright}s Hospital Foundation and the Department of Pediatrics Research Enterprise (University of Utah). We also acknowledge Aaron Bretones and Niraja Bhachech for lab support, and we acknowledge Niraja Bhachech and Jared Fowles for their advice and critical review of this manuscript. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number U54CA217376. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We acknowledge Cell Imaging Core at the University of Utah for use of NIS-Elements AR Analysis and the Flow Cytometry Core at the University of Utah who are supported by the Office of the Director of the National Institutes of Health under Award Number S10OD026959. Sequencing was performed at the DNA Sequencing Core Facility, University of Utah. We would also like to thank Sir. David Lane, Laura Attardi, Carol Prives, Bradley Cairns, and Martin McMahon for their guidance. Funding Information: JDS received funding from Hyundai Motor Group | Hyundai Motor America | Hyundai Hope On Wheels (Hope On Wheels), U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) - U54CA217376, and Soccer for Hope Foundation, Li-Fraumeni Syndrome Association, Kneaders Hope Fights Childhood Cancer. LMA received funding from Primary Children{\textquoteright}s Hospital Foundation and University of Utah Department of Pediatrics Research Enterprise. Publisher Copyright: {\textcopyright} 2023, The Author(s).",
year = "2023",
month = dec,
doi = "10.1038/s41420-023-01348-7",
language = "English (US)",
volume = "9",
journal = "Cell Death Discovery",
issn = "2058-7716",
publisher = "Nature Publishing Group",
number = "1",
}