Elephant TP53-RETROGENE 9 induces transcription-independent apoptosis at the mitochondria.
Journal
Cell death discovery
ISSN: 2058-7716
Titre abrégé: Cell Death Discov
Pays: United States
ID NLM: 101665035
Informations de publication
Date de publication:
16 Feb 2023
16 Feb 2023
Historique:
received:
01
02
2022
accepted:
30
01
2023
revised:
24
01
2023
entrez:
16
2
2023
pubmed:
17
2
2023
medline:
17
2
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 36797268
doi: 10.1038/s41420-023-01348-7
pii: 10.1038/s41420-023-01348-7
pmc: PMC9935553
doi:
Types de publication
Journal Article
Langues
eng
Pagination
66Subventions
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : U54CA217376
Informations de copyright
© 2023. The Author(s).
Références
iScience. 2020 Aug 21;23(8):101373
pubmed: 32738614
Mol Cell. 2003 Mar;11(3):577-90
pubmed: 12667443
Cancers (Basel). 2021 Aug 25;13(17):
pubmed: 34503094
Cancer Cell. 2003 Nov;4(5):371-81
pubmed: 14667504
Trends Ecol Evol. 2011 Apr;26(4):175-82
pubmed: 21296451
EMBO J. 2007 Feb 21;26(4):923-34
pubmed: 17268548
Pharmacol Ther. 2019 Oct;202:149-164
pubmed: 31276706
Nature. 1994 Jul 21;370(6486):220-3
pubmed: 8028670
Mol Biol Evol. 2021 Aug 23;38(9):3606-3620
pubmed: 33944920
Mol Cells. 2014 Mar;37(3):264-9
pubmed: 24646834
Oncotarget. 2010 Oct;1(6):396-404
pubmed: 21311096
Nat Cell Biol. 2004 May;6(5):443-50
pubmed: 15077116
Mol Pharm. 2012 May 7;9(5):1449-58
pubmed: 22380534
Nature. 2005 Mar 31;434(7033):652-8
pubmed: 15800626
J Biol Chem. 2000 May 26;275(21):16202-12
pubmed: 10821866
J Biol Chem. 2006 Mar 31;281(13):8600-6
pubmed: 16443602
Biochemistry. 2013 Sep 17;52(37):6324-34
pubmed: 23977882
Science. 1996 Nov 8;274(5289):948-53
pubmed: 8875929
Nat Rev Mol Cell Biol. 2012 Jan 18;13(2):89-102
pubmed: 22251901
Cell Rep. 2014 Apr 10;7(1):104-12
pubmed: 24703847
Curr Cancer Drug Targets. 2009 Nov;9(7):871-80
pubmed: 20025574
Genes Dev. 1994 Dec 1;8(23):2817-30
pubmed: 7995520
JAMA. 2015 Nov 3;314(17):1850-60
pubmed: 26447779
Oncogene. 2010 Feb 25;29(8):1155-66
pubmed: 19935715
J Biol Chem. 2008 Jul 25;283(30):21294-304
pubmed: 18524770
Nat Struct Mol Biol. 2014 Jun;21(6):535-43
pubmed: 24814347
Br J Cancer. 1975 Oct;32(4):411-26
pubmed: 1212409
Cell. 2017 Sep 7;170(6):1062-1078
pubmed: 28886379
Mol Cell Biol. 1990 Dec;10(12):6565-77
pubmed: 2247074
Cell Rep. 2018 Aug 14;24(7):1765-1776
pubmed: 30110634
EMBO J. 1998 Jun 15;17(12):3342-50
pubmed: 9628871
J Biol Chem. 2007 Oct 5;282(40):29193-200
pubmed: 17699158
Cell. 1993 Nov 19;75(4):817-25
pubmed: 8242752
Elife. 2016 Sep 19;5:
pubmed: 27642012
Am J Physiol Cell Physiol. 2011 Apr;300(4):C723-42
pubmed: 21209361
Pharm Res. 2014 Sep;31(9):2503-15
pubmed: 24633417
Cancer Discov. 2019 Jan;9(1):46-63
pubmed: 30266815
Science. 2004 Feb 13;303(5660):1010-4
pubmed: 14963330
Genes Dev. 1995 Sep 1;9(17):2170-83
pubmed: 7657168
Oncogene. 2000 Dec 14;19(54):6216-28
pubmed: 11175336
Science. 1995 Mar 10;267(5203):1498-502
pubmed: 7878469
Cytometry A. 2010 Aug;77(8):733-42
pubmed: 20653013
Mol Biol Evol. 2022 Jul 2;39(7):
pubmed: 35792674
Mol Pharm. 2013 Oct 7;10(10):3592-602
pubmed: 23968395
Cell Rep. 2018 Mar 6;22(10):2742-2755
pubmed: 29514101