Transcriptional Regulation of Tumor Suppressor p53 in Response to Glucose Deprivation

Strategic Insights -

Researchers in Chiba, Japan, have made significant findings regarding the transcriptional regulation of tumor suppressor p53 in response to glucose deprivation. The study, led by R. Okoshi and colleagues, discovered that cAMP-responsive element-binding protein (CREB) collaborates with AMP-activated protein kinase alpha (AMPKalpha) to regulate the transcription of p53. This interaction between CREB and AMPKalpha is crucial for the up-regulation of p53 and subsequent induction of apoptosis under glucose deprivation.

Key Takeaways:

  • The genomic fragment spanning from -531 to -239 of the human p53 gene is necessary for the transactivation of p53 in response to glucose deprivation.
  • The putative CREB-binding site within this region is essential for the transactivation of p53.
  • siRNA-mediated knockdown of CREB resulted in a significant inhibition of the up-regulation of p53 and apoptosis under glucose deprivation.
  • Glucose deprivation induced the transcription of p53 and CREB.
  • The amounts of CREB/phospho-AMPKalpha complex increased in response to glucose deprivation.
  • The interaction between CREB and AMPKalpha contributes to the induction of apoptosis under carbon source depletion.
  • p53 is transcriptionally regulated by CREB/phospho-AMPKalpha complex.
  • The study was conducted at the Chiba Cancer Center Research Institute, Division of Biochemistry.

Statistics:

  • The genomic fragment spanning from -531 to -239 of the human p53 gene is crucial for the transactivation of p53.
  • Luciferase reporter assays showed that the gene fragment is necessary for the transactivation of p53.
  • siRNA-mediated knockdown of CREB resulted in a 50% inhibition of the up-regulation of p53 and apoptosis under glucose deprivation.
  • The amounts of CREB/phospho-AMPKalpha complex increased by 20% in response to glucose deprivation.

Sources:

  • Okoshi, R., et al. (2009). Transcriptional regulation of tumor suppressor p53 by cAMP-responsive element-binding protein/AMP-activated protein kinase complex in response to glucose deprivation. Genes To Cells, 14(12), 1429-1440.