Sp1-like sequences mediate human caspase-3 promoter activation by p73 and cisplatin

FEBS J. 2008 May;275(9):2200-13. doi: 10.1111/j.1742-4658.2008.06373.x. Epub 2008 Apr 1.


Caspase-3 is a cysteine protease that plays a central role in the execution of apoptosis induced by a wide variety of stimuli. However, little is known about the mechanisms involved in the regulation of caspase-3 gene transcription. This study was carried out to characterize the human caspase-3 promoter and to understand the mechanisms involved in the induction of caspase-3 gene expression in response to the anticancer drug cisplatin and p73. Caspase-3 gene expression was induced by treatment of cells with cisplatin, which also induced p73 protein in HeLa and K562 cells. The human caspase-3 promoter was cloned and characterized. p73beta strongly activated the caspase-3 promoter, whereas p73alpha showed less activation. Cisplatin treatment increased caspase-3 promoter activity. Basal and cisplatin-induced promoter activity was inhibited by the p73 inhibitor p73DD. Deletion analysis defined a minimal promoter of 120 base pairs, which showed good basal and p73beta-induced activity. The examination of the minimal promoter sequence showed several putative Sp1 sites, but no p53/p73 site. The caspase-3 promoter was activated by Sp1 in Sp1-deficient Drosophila SL-2 cells. Sp1-induced promoter activity was further enhanced by p73beta in SL-2 cells. Mutation of Sp1 sites in the minimal promoter resulted in a loss of basal and p73-induced promoter activity. These results show that caspase-3 gene transcription is induced by cisplatin, which is mediated partly by p73. We have identified p73 and Sp1 as activators of the caspase-3 promoter. Sp1-like sequences in the minimal promoter not only sustain basal promoter activity, but also mediate p73-induced activation of the promoter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Base Pairing
  • Base Sequence
  • Binding Sites
  • Caspase 3 / genetics*
  • Cisplatin / pharmacology*
  • DNA-Binding Proteins / physiology*
  • Enzyme Activation
  • Genes, Reporter
  • HeLa Cells
  • Humans
  • K562 Cells
  • Nuclear Proteins / physiology*
  • Promoter Regions, Genetic*
  • RNA, Messenger / analysis
  • Sequence Homology, Nucleic Acid
  • Sp1 Transcription Factor / chemistry*
  • Sp1 Transcription Factor / metabolism
  • Transcription, Genetic / drug effects
  • Tumor Protein p73
  • Tumor Suppressor Proteins / physiology*


  • Antineoplastic Agents
  • DNA-Binding Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • Sp1 Transcription Factor
  • TP73 protein, human
  • Tumor Protein p73
  • Tumor Suppressor Proteins
  • Caspase 3
  • Cisplatin