ATF5 ELISA Kit

Asparagine synthetase catalyses the glutamine- and ATP-dependent conversion of aspartic acid to asparagine. In human hepatoma cells cultured in medium containing amino acids, the mRNA of asparagine synthetase is not detectable by RNase protection mapping. However, maintaining the cells in amino acid-free Krebs-Ringer bicarbonate buffer strongly upregulated asparagine synthetase biosynthesis. The effect of amino acid deprivation on asparagine synthetase gene transcription is mediated by a genetic element termed the nutrient-sensing response unit. Previous studies revealed that the basic region leucine zipper (bZIP) transcription factor CREB2/ATF4 is involved in the nutrient deprivation-induced upregulation of asparagine synthetase gene transcription. Here we show that overexpression of the bZIP protein ATF5, a transcriptional activator, stimulates asparagine synthetase promoter/reporter gene transcription via the nutrient-sensing response unit. In contrast, ATF5 does not transactivate cAMP response element (CRE)-containing reporter genes. Overexpression of the C/EBP homologous transcription factor CHOP impaired transcriptional activation of the asparagine synthetase promoter following amino acid deprivation or overexpression of ATF5 or CREB2/ATF4. These data indicate that CHOP functions as a shut-off-device for nutrient deprivation-induced gene transcription.

The expression of activating transcription factor 5 (ATF5) correlates negatively with patient survival in different types of cancer. ATF5 is important for the survival and proliferation of cancer cells, and can be targeted to selectively trigger cancer cell apoptosis while sparing normal cells. Cell-penetrating peptides combined with a dominant negative ATF5 cargo have recently shown efficacy against brain, breast, melanoma, and prostate cancers.