Transcriptional upregulation of PUMA modulates endoplasmic reticulum calcium pool depletion-induced apoptosis via Bax activation
- PMID: 15905879
- DOI: 10.1038/sj.cdd.4401659
Transcriptional upregulation of PUMA modulates endoplasmic reticulum calcium pool depletion-induced apoptosis via Bax activation
Abstract
PUMA, a key mediator of p53-induced apoptosis, is a BH3-only domain proapoptotic protein that localizes to mitochondria and interacts with antiapoptotic Bcl-2 and Bcl-X(L). Recent evidence implicates Bax to be an important mediator of PUMA-activated apoptotic signals. We have previously demonstrated that Bax deficiency significantly affects thapsigargin (TG)-mediated endoplasmic reticulum calcium pool depletion-induced apoptosis. We now present evidence that TG upregulates PUMA expression and that although Bax-deficient cells exhibit resistance to TG, Bax deficiency does not attenuate TG upregulation of PUMA expression. Furthermore, TG transcriptionally upregulates PUMA expression in a p53-independent manner and that PUMA-deficient cells are more resistant to undergo TG-induced apoptosis than the PUMA-proficient counterparts. Thus, our results demonstrate that TG engages PUMA and Bax for full transduction of apoptotic signals and both PUMA and Bax appear to exist in the same TG-activated apoptotic pathway in which PUMA may reside upstream of Bax.
Similar articles
-
Effect of Bax deficiency on death receptor 5 and mitochondrial pathways during endoplasmic reticulum calcium pool depletion-induced apoptosis.Oncogene. 2003 May 1;22(17):2674-9. doi: 10.1038/sj.onc.1206363. Oncogene. 2003. PMID: 12730681
-
p73 Induces apoptosis via PUMA transactivation and Bax mitochondrial translocation.J Biol Chem. 2004 Feb 27;279(9):8076-83. doi: 10.1074/jbc.M307469200. Epub 2003 Nov 21. J Biol Chem. 2004. PMID: 14634023
-
Regulation of Bax activation and apoptotic response to microtubule-damaging agents by p53 transcription-dependent and -independent pathways.J Biol Chem. 2004 Sep 17;279(38):39431-7. doi: 10.1074/jbc.M401530200. Epub 2004 Jul 19. J Biol Chem. 2004. PMID: 15262986
-
Mechanism of induction of apoptosis by p73 and its relevance to neuroblastoma biology.Ann N Y Acad Sci. 2004 Dec;1028:143-9. doi: 10.1196/annals.1322.015. Ann N Y Acad Sci. 2004. PMID: 15650240 Review.
-
PUMA, a critical mediator of cell death--one decade on from its discovery.Cell Mol Biol Lett. 2012 Dec;17(4):646-69. doi: 10.2478/s11658-012-0032-5. Epub 2012 Sep 20. Cell Mol Biol Lett. 2012. PMID: 23001513 Free PMC article. Review.
Cited by
-
BH3-only proapoptotic Bcl-2 family members Noxa and Puma mediate neural precursor cell death.J Neurosci. 2006 Jul 5;26(27):7257-64. doi: 10.1523/JNEUROSCI.0196-06.2006. J Neurosci. 2006. PMID: 16822983 Free PMC article.
-
Calcium trafficking integrates endoplasmic reticulum function with mitochondrial bioenergetics.Biochim Biophys Acta. 2014 Oct;1843(10):2233-9. doi: 10.1016/j.bbamcr.2014.03.022. Epub 2014 Mar 30. Biochim Biophys Acta. 2014. PMID: 24690484 Free PMC article. Review.
-
Deletion of the pro-apoptotic endoplasmic reticulum stress response effector CHOP does not result in improved locomotor function after severe contusive spinal cord injury.J Neurotrauma. 2012 Feb 10;29(3):579-88. doi: 10.1089/neu.2011.1940. Epub 2011 Nov 21. J Neurotrauma. 2012. PMID: 21933012 Free PMC article.
-
Multimodal interaction with BCL-2 family proteins underlies the proapoptotic activity of PUMA BH3.Chem Biol. 2013 Jul 25;20(7):888-902. doi: 10.1016/j.chembiol.2013.06.007. Chem Biol. 2013. PMID: 23890007 Free PMC article.
-
HER2 phosphorylates and destabilizes pro-apoptotic PUMA, leading to antagonized apoptosis in cancer cells.PLoS One. 2013 Nov 13;8(11):e78836. doi: 10.1371/journal.pone.0078836. eCollection 2013. PLoS One. 2013. PMID: 24236056 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous
