PMID- 15905879 OWN - NLM STAT- MEDLINE DCOM- 20051110 LR - 20161124 IS - 1350-9047 (Print) IS - 1350-9047 (Linking) VI - 12 IP - 10 DP - 2005 Oct TI - Transcriptional upregulation of PUMA modulates endoplasmic reticulum calcium pool depletion-induced apoptosis via Bax activation. PG - 1310-8 AB - 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. FAU - Luo, X AU - Luo X AD - Department of Pharmacology, State University of New York, Upstate Medical University, Syracuse, NY 13210, USA. FAU - He, Q AU - He Q FAU - Huang, Y AU - Huang Y FAU - Sheikh, M S AU - Sheikh MS LA - eng GR - CA86945/CA/NCI NIH HHS/United States GR - DK062136/DK/NIDDK NIH HHS/United States GR - DK067271/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Cell Death Differ JT - Cell death and differentiation JID - 9437445 RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (BAX protein, human) RN - 0 (BBC3 protein, human) RN - 0 (DNA-Binding Proteins) RN - 0 (Nuclear Proteins) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (Tumor Protein p73) RN - 0 (Tumor Suppressor Protein p53) RN - 0 (Tumor Suppressor Proteins) RN - 0 (bcl-2-Associated X Protein) RN - 67526-95-8 (Thapsigargin) RN - SY7Q814VUP (Calcium) SB - IM MH - Apoptosis/drug effects/*physiology/radiation effects MH - Apoptosis Regulatory Proteins MH - Base Sequence MH - Calcium/deficiency/*metabolism MH - Cell Line, Tumor MH - DNA-Binding Proteins/deficiency/metabolism MH - Endoplasmic Reticulum/*metabolism MH - Genes, Tumor Suppressor MH - HCT116 Cells MH - Humans MH - Male MH - Molecular Sequence Data MH - Nuclear Proteins/deficiency/metabolism MH - Proto-Oncogene Proteins/*metabolism MH - Proto-Oncogene Proteins c-bcl-2/deficiency/*metabolism MH - Thapsigargin/pharmacology MH - Transcription, Genetic/drug effects MH - Tumor Protein p73 MH - Tumor Suppressor Protein p53/*metabolism MH - Tumor Suppressor Proteins MH - Up-Regulation/drug effects MH - bcl-2-Associated X Protein EDAT- 2005/05/21 09:00 MHDA- 2005/11/11 09:00 CRDT- 2005/05/21 09:00 PHST- 2005/05/21 09:00 [pubmed] PHST- 2005/11/11 09:00 [medline] PHST- 2005/05/21 09:00 [entrez] AID - 4401659 [pii] AID - 10.1038/sj.cdd.4401659 [doi] PST - ppublish SO - Cell Death Differ. 2005 Oct;12(10):1310-8. doi: 10.1038/sj.cdd.4401659.