Transcriptional repressor activating transcription factor 3 protects human umbilical vein endothelial cells from tumor necrosis factor-alpha-induced apoptosis through down-regulation of p53 transcription
- PMID: 12161427
- DOI: 10.1074/jbc.M202974200
Transcriptional repressor activating transcription factor 3 protects human umbilical vein endothelial cells from tumor necrosis factor-alpha-induced apoptosis through down-regulation of p53 transcription
Abstract
Activating transcription factor 3 (ATF3) is a transcriptional repressor that is rapidly induced in cells exposed to a wide range of stress stimuli. To clarify the role of ATF3 in determining cell fate, we overexpressed it in human umbilical vein endothelial cells (HUVECs) by adenovirus-mediated gene transfer. ATF3 protected these cells from tumor necrosis factor (TNF)-alpha-induced apoptosis, as measured by flow cytometric analysis, trypan blue exclusion assay, and cleavage of procaspase 3 and poly(ADP-ribose) polymerase. Northern blot and nuclear run on assay showed that the transcription of tumor suppressor gene p53 was down-regulated in the ATF3-overexpressing cells. In the transient expression assay, ATF3 suppressed the p53 gene promoter activity through its specific binding to an atypical AP-1 element, PF-1 site, in the p53 gene promoter. Furthermore, the cell-protecting effect of ATF3 was remarkably reduced in p53-deficient cells. These results demonstrate that overexpression of ATF3 suppresses TNF-alpha-induced cell death of HUVECs, at least in part, through down-regulating the transcription of p53 gene. ATF3 may function as a cell survival factor of endothelial cells during vascular inflammation and atherogenesis.
Similar articles
-
Expression of transcriptional repressor ATF3/LRF1 in human atherosclerosis: colocalization and possible involvement in cell death of vascular endothelial cells.Atherosclerosis. 2002 Apr;161(2):281-91. doi: 10.1016/s0021-9150(01)00639-6. Atherosclerosis. 2002. PMID: 11888510
-
Overexpression of Ref-1 inhibits hypoxia and tumor necrosis factor-induced endothelial cell apoptosis through nuclear factor-kappab-independent and -dependent pathways.Circ Res. 2001 Jun 22;88(12):1247-53. doi: 10.1161/hh1201.091796. Circ Res. 2001. PMID: 11420300
-
Transcriptional activation of the human stress-inducible transcriptional repressor ATF3 gene promoter by p53.Biochem Biophys Res Commun. 2002 Oct 11;297(5):1302-10. doi: 10.1016/s0006-291x(02)02382-3. Biochem Biophys Res Commun. 2002. PMID: 12372430
-
New insights into p53 activation.Cell Res. 2010 Jun;20(6):614-21. doi: 10.1038/cr.2010.53. Epub 2010 Apr 20. Cell Res. 2010. PMID: 20404858 Free PMC article. Review.
-
One function--multiple mechanisms: the manifold activities of p53 as a transcriptional repressor.J Biomed Biotechnol. 2011;2011:464916. doi: 10.1155/2011/464916. Epub 2011 Mar 8. J Biomed Biotechnol. 2011. PMID: 21436991 Free PMC article. Review.
Cited by
-
Semaphorin 7A promotes endothelial to mesenchymal transition through ATF3 mediated TGF-β2/Smad signaling.Cell Death Dis. 2020 Aug 10;11(8):695. doi: 10.1038/s41419-020-02818-x. Cell Death Dis. 2020. PMID: 32826874 Free PMC article.
-
Screening of differentially expressed proteins from syncytiotrophoblast for severe early-onset preeclampsia in women with gestational diabetes mellitus using tandem mass tag quantitative proteomics.BMC Pregnancy Childbirth. 2018 Nov 7;18(1):437. doi: 10.1186/s12884-018-2066-9. BMC Pregnancy Childbirth. 2018. PMID: 30404616 Free PMC article.
-
Learning common and specific patterns from data of multiple interrelated biological scenarios with matrix factorization.Nucleic Acids Res. 2019 Jul 26;47(13):6606-6617. doi: 10.1093/nar/gkz488. Nucleic Acids Res. 2019. PMID: 31175825 Free PMC article.
-
Role of activating transcription factor 3 (ATF3) in endoplasmic reticulum (ER) stress-induced sensitization of p53-deficient human colon cancer cells to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis through up-regulation of death receptor 5 (DR5) by zerumbone and celecoxib.J Biol Chem. 2014 Aug 1;289(31):21544-61. doi: 10.1074/jbc.M114.558890. Epub 2014 Jun 17. J Biol Chem. 2014. PMID: 24939851 Free PMC article.
-
Defining the antigen receptor-dependent regulatory network that induces arrest of cycling immature B-lymphocytes.BMC Syst Biol. 2010 Dec 9;4:169. doi: 10.1186/1752-0509-4-169. BMC Syst Biol. 2010. PMID: 21143896 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Research Materials
Miscellaneous
