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:
IAPinhibitor of apoptosisGAPDHglyceraldehyde-3-phosphate dehydrogenaseCDEcell cycle-dependent elementsHDAChistone deacetylaseAbantibodyPARPpoly(ADP) ribose polymeraseCMVcytomegalovirus
High - Quality Tools Life Scientists Use to Seek Answers
Reagent " Tool Kits"
Specific combinations of chemistries that allow customers to carry out laboratory tests in the fields of cell biology; DNA, RNA and protein analysis; drug development; human identification; and molecular diagnostics.
Integrated Systems
Instrumentation that allows customers to automate their various research and lab procedures, increasing efficiency and precision.
Where Our Products Are Used
Pharmaceutical and Biotechnology Industries
Discovering new drugs to fight disease
Clinical and Molecular Diagnostics Laboratories
Detecting disease and determining therapies
Forensics and Paternity Laboratories
Discovering new drugs to fight disease
Government and Academic Research Laboratories
Discovering new drugs to fight disease
Applied Testing
Ensuring environmental food, water and plant safety and quality
Our Living Values
We have a 100 year mindset to keep asking questions that change the world. Promega exists on an evolutionary frontier where the values of science, business and human well-being intersect.
Read more about our purpose and values.
Integrated Systems
Instrumentation that allows customers to automate their various research and lab procedures, increasing efficiency and precision.
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:
IAPinhibitor of apoptosisGAPDHglyceraldehyde-3-phosphate dehydrogenaseCDEcell cycle-dependent elementsHDAChistone deacetylaseAbantibodyPARPpoly(ADP) ribose polymeraseCMVcytomegalovirus