Tid1 is a new regulator of p53 mitochondrial translocation and apoptosis in cancer
- PMID: 19935715
- DOI: 10.1038/onc.2009.413
Tid1 is a new regulator of p53 mitochondrial translocation and apoptosis in cancer
Abstract
The p53 tumor suppressor protein induces apoptosis in response to genotoxic and environmental stresses. Recent studies have revealed the existence of a transcription-independent mitochondrial p53 apoptotic pathway; however, the mechanism that regulates its translocation to the mitochondria has been unknown. In this study, we show that the tumor suppressor Tid1 forms a complex with p53 under hypoxic conditions that directs p53 translocation to the mitochondria and the subsequent initiation of the mitochondrial apoptosis pathway. Loss of Tid1 expression abrogated p53 translocation to the mitochondria and inhibited apoptosis, whereas the over-expression of Tid1 promoted p53 mitochondrial localization and apoptosis. Tid1's mitochondrial signal sequence and DnaJ domain were both required for the movement of the p53-Tid1 complex from the cytosol to the mitochondria. When Tid is over-expressed in cancer cell lines expressing mutant p53 isoforms defective in transcriptional activity, mitochondrial localization and pro-apoptotic activities of the mutant p53 proteins was restored. Our results establish Tid1 as a novel regulator of p53-mediated apoptosis, and suggest that therapies designed to enhance Tid1's function in promoting mitochondrial localization of p53 and apoptosis could be an effective therapy in many cancers.
Similar articles
-
Direct interaction between p53 and Tid1 proteins affects p53 mitochondrial localization and apoptosis.Oncotarget. 2010 Oct;1(6):396-404. doi: 10.18632/oncotarget.174. Oncotarget. 2010. PMID: 21311096 Free PMC article.
-
ASC is a Bax adaptor and regulates the p53-Bax mitochondrial apoptosis pathway.Nat Cell Biol. 2004 Feb;6(2):121-8. doi: 10.1038/ncb1087. Epub 2004 Jan 18. Nat Cell Biol. 2004. PMID: 14730312
-
Involvement of Bcl-2 family members, phosphatidylinositol 3'-kinase/AKT and mitochondrial p53 in curcumin (diferulolylmethane)-induced apoptosis in prostate cancer.Int J Oncol. 2007 Apr;30(4):905-18. Int J Oncol. 2007. PMID: 17332930
-
Stress-induced p53 runs a transcription-independent death program.Biochem Biophys Res Commun. 2005 Jun 10;331(3):843-50. doi: 10.1016/j.bbrc.2005.03.187. Biochem Biophys Res Commun. 2005. PMID: 15865940 Review.
-
Transcription-independent pro-apoptotic functions of p53.Curr Opin Cell Biol. 2005 Dec;17(6):631-6. doi: 10.1016/j.ceb.2005.09.007. Epub 2005 Oct 13. Curr Opin Cell Biol. 2005. PMID: 16226451 Review.
Cited by
-
Nuclear-Mitochondrial Interactions.Biomolecules. 2022 Mar 10;12(3):427. doi: 10.3390/biom12030427. Biomolecules. 2022. PMID: 35327619 Free PMC article. Review.
-
DRAM1 increases the secretion of PKM2-enriched EVs from hepatocytes to promote macrophage activation and disease progression in ALD.Mol Ther Nucleic Acids. 2021 Dec 11;27:375-389. doi: 10.1016/j.omtn.2021.12.017. eCollection 2022 Mar 8. Mol Ther Nucleic Acids. 2021. PMID: 35036051 Free PMC article.
-
ING1 induces apoptosis through direct effects at the mitochondria.Cell Death Dis. 2013 Sep 5;4(9):e788. doi: 10.1038/cddis.2013.321. Cell Death Dis. 2013. PMID: 24008732 Free PMC article.
-
ATF4 Signaling in HIV-1 Infection: Viral Subversion of a Stress Response Transcription Factor.Biology (Basel). 2024 Feb 26;13(3):146. doi: 10.3390/biology13030146. Biology (Basel). 2024. PMID: 38534416 Free PMC article. Review.
-
LACE1 interacts with p53 and mediates its mitochondrial translocation and apoptosis.Oncotarget. 2016 Jul 26;7(30):47687-47698. doi: 10.18632/oncotarget.9959. Oncotarget. 2016. PMID: 27323408 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous
