Abstract
Recruitment of the coactivator, CREB binding protein (CBP), by signal-regulated transcription factors, such as CREB [adenosine 3', 5'-monophosphate (cAMP) response element binding protein], is critical for stimulation of gene expression. The mouse pituitary cell line AtT20 was used to show that the CBP recruitment step (CREB phosphorylation on serine-133) can be uncoupled from CREB/CBP-activated transcription. CBP was found to contain a signal-regulated transcriptional activation domain that is controlled by nuclear calcium and calcium/calmodulin-dependent (CaM) protein kinase IV and by cAMP. Cytoplasmic calcium signals that stimulate the Ras mitogen-activated protein kinase signaling cascade or expression of the activated form of Ras provided the CBP recruitment signal but did not increase CBP activity and failed to activate CREB- and CBP-mediated transcription. These results identify CBP as a signal-regulated transcriptional coactivator and define a regulatory role for nuclear calcium and cAMP in CBP-dependent gene expression.
| Original language | English |
|---|---|
| Pages (from-to) | 1505-9 |
| Number of pages | 5 |
| Journal | Science |
| Volume | 281 |
| Issue number | 5382 |
| Publication status | Published - 1998 |
Keywords
- Animals
- CREB-Binding Protein
- Calcium
- Calcium Channels
- Calcium-Calmodulin-Dependent Protein Kinase Type 2
- Calcium-Calmodulin-Dependent Protein Kinase Type 4
- Calcium-Calmodulin-Dependent Protein Kinases
- Cell Line
- Cell Nucleus
- Cyclic AMP
- Cyclic AMP Response Element-Binding Protein
- Cytoplasm
- Genes, Reporter
- Mice
- Models, Genetic
- Nuclear Proteins
- Phosphorylation
- Phosphoserine
- Recombinant Fusion Proteins
- Signal Transduction
- Trans-Activators
- Transcription, Genetic
- Transcriptional Activation
- ras Proteins