A role for the non-conserved N-terminal domain of the TATA-binding protein in the crosstalk between cell signaling pathways and steroid receptors

Abstract

Transcriptional induction by steroid receptors is coupled to cellular signal transduction pathways although, in general, the mechanisms governing these events are not well defined. Using TATA-binding protein (TBP) specificity mutants that recognize a TGTA box, we show that yeast TBP expressed in mammalian cells can support steroid-mediated gene induction to a similar degree as human TBP, however yeast TBP does not support the 8-Bromo-cAMP-mediated potentiation of glucocorticoid receptor (GR)-dependent transactivation. Chimeras between yeast and human TBP reveal that it is the non-conserved N-terminus of TBP that governs the potentiation of GR action. While the conserved core of TBP is sufficient for TATA-element binding and preinitiation complex formation, the role of the N-terminus has remained elusive. Our results suggest a role of the N-terminus of human TBP in coupling cell signaling events to steroid-mediated transcription, thereby establishing one of the few described functional roles of this polypeptide domain in a physiological process.

Keywords

• TBP
• glucocorticoid receptor
• cyclic AMP
• steroid receptor
• coactivator
• crosstalk
• protein kinase A