Sp1 and p73 activate PUMA following serum starvation
- 13 March 2008
- journal article
- Published by Oxford University Press (OUP) in Carcinogenesis: Integrative Cancer Research
- Vol. 29 (10), 1878-1884
- https://doi.org/10.1093/carcin/bgn150
Abstract
P53-upregulated modulator of apoptosis (PUMA) plays an essential role in p53-dependent apoptosis following DNA damage. PUMA also mediates apoptosis independent of p53. In this study, we investigated the role and mechanism of PUMA induction in response to serum starvation in p53-deficient cancer cells. Following serum starvation, the binding of Sp1 to the PUMA promoter significantly increased, whereas inhibition of Sp1 completely abrogated PUMA induction. p73 was found to be upregulated by serum starvation and mediate PUMA induction through the p53-binding sites in the PUMA promoter. Sp1 and p73beta appeared to cooperatively activate PUMA transcription, which is inhibited by the phosphoinsitide 3-kinase (PI3K)-protein kinase B (AKT) pathway. Furthermore, knockdown of PUMA suppressed serum starvation-induced apoptosis in leukemia cells. Our results suggest that transcription factors Sp1 and p73 mediate p53-independent induction of PUMA following serum starvation to trigger apoptosis in human cancer cells.Keywords
This publication has 49 references indexed in Scilit:
- p53 independent induction of PUMA mediates intestinal apoptosis in response to ischaemia-reperfusionGut, 2007
- The nuclear function of p53 is required for PUMA-mediated apoptosis induced by DNA damageProceedings of the National Academy of Sciences of the United States of America, 2007
- Cell death provoked by loss of interleukin-3 signaling is independent of Bad, Bim, and PI3 kinase, but depends in part on PumaBlood, 2006
- The NF-κB regulator Bcl-3 and the BH3-only proteins Bim and Puma control the death of activated T cellsProceedings of the National Academy of Sciences, 2006
- FOXO3a-dependent regulation of Puma in response to cytokine/growth factor withdrawalThe Journal of Experimental Medicine, 2006
- The transcriptional targets of p53 in apoptosis controlBiochemical and Biophysical Research Communications, 2005
- Cyclin-dependent Kinases Phosphorylate p73 at Threonine 86 in a Cell Cycle-dependent Manner and Negatively Regulate p73Published by Elsevier BV ,2003
- Live or let die: the cell's response to p53Nature Reviews Cancer, 2002
- The Hallmarks of CancerCell, 2000
- Features in the 5′ non-coding sequences of rabbit α and β-globin mRNAs that affect translational efficiencyJournal of Molecular Biology, 1994