Transcriptional Repression of the Anti-apoptoticsurvivin Gene by Wild Type p53*

By William H. Hoffman, S. Biade, J. T. Zilfou, Jiandong Chen, M. Murphy. Journal of Biological Chemistry, 2002

854 citations recorded by the source corpus.

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.

Subfields: Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/c4f4e293a1ff83757466d996711768ab3f690070

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Citations in the corpus

p53 induces differentiation of mouse embryonic stem cells by suppressing Nanog expression (2005, background): “These putative p53 response elements contain a two- and six-nucleotide spacer, respectively, between the two 'half' sites of the p53-binding sites; this feature is consistent with the p53-binding sites involved in p53-dependent transcriptional repressio”
Decision making by p53: life, death and cancer (2003, background): “Subsequently, p53 was shown to repress the Bcl-X promoter,(57) and the latest to join this list is survivin.(58,59) Most certainly, additional candidates will emerge with time.”
Transcriptional control of human p53-regulated genes (2008, background): “One model proposes that the switch between p53-mediated activation and repression is determined by the length of the space”
Control of apoptosis by p53 (2003, background): “In principle, p53 mutations might contribute to the high frequency of Survivin overexpression observed in human tumors (Hoffman et al., 2002).”
Radiation-induced cell death mechanisms (2010, background): “P53 can mediate transcriptional repression of anti-apoptotic genes including the Bcl-2 gene [49, 50] and the inhibitor of apoptosis protein-family member survivin [ 51 , 52].”