Reference - Merck Millipore

Transcriptional Repression of the Anti-apoptoticsurvivin Gene by Wild …

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Abstract

Survivin is a member of the inhibitor of apoptosis family. This apoptosis inhibitor also has an evolutionarily conserved role as a mitotic spindle checkpoint protein. Previous studies on p53-repressed genes have implicated several genes involved in the G2/M transition of the cell cycle as targets of negative regulation by p53. However, few targets of p53 repression that are anti-apoptotic have been identified. This study identifies the anti-apoptotic survivin gene as a p53-repressed gene. Notably, Survivin repression by p53 is shown to be distinct from p53-dependent growth arrest. Chromatin immunoprecipitations indicate that p53 binds the survivinpromoter in vivo; immunobinding studies indicate that this site overlaps with a binding site for E2F transcription factors and is subtly distinct from a canonical p53-transactivating element. Thesurvivin-binding site contains a 3-nucleotide spacer between the two decamer “half-sites” of the p53 consensus element; deletion of this spacer is sufficient to convert thesurvivin site into a transactivating element. Finally, we show that overexpression of Survivin in cells sensitive to p53-dependent cell death markedly inhibits apoptosis induced by ultraviolet light. The identification ofsurvivin as a p53 repressed gene should aid in the elucidation of the contribution of transcriptional repression to p53-dependent apoptosis.

Abbreviations:
IAP
inhibitor of apoptosis
GAPDH
glyceraldehyde-3-phosphate dehydrogenase
CDE
cell cycle-dependent elements
HDAC
histone deacetylase
Ab
antibody
PARP
poly(ADP) ribose polymerase
CMV
cytomegalovirus
  • Received July 16, 2001.
  • Revision received November 6, 2001.

 

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