Activated cAMP-response element-binding protein regulates neuronal expression of presenilin-1.
Journal Article (Journal Article)
Upon binding to the cAMP-response element of a gene's promoter, the transcription factor known as cAMP-response element-binding protein (CREB) facilitates transcription of many different neuronal genes including those involved with synaptic function. Based on our previous reports of gene structure (GenBank accession number AF029701 ), we now demonstrate that activated CREB binds to the proximal promoter of the human presenilin-1 (PS-1) gene to activate PS-1 transcription in rat and in human neuronal cells. Specific stimulation of the N-methyl-d-aspartate subtype of neuronal glutamate receptors activates CREB and results in increased PS-1 expression. Similarly, treatment with brain-derived neurotrophic factor activates CREB and increases PS-1 expression in a dose-dependent fashion. By using adenovirus vectors expressing dominant negative forms of CREB, we were able to show that induction of PS-1 expression requires the activation of CREB. Conversely, constitutive expression of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK) results in activation of CREB and increased PS-1 expression that can be blocked by the addition of selective MEK inhibitors. Our findings suggest a hypothesis where stimulation of N-methyl-d-aspartate receptors signals CREB activation to enhance PS-1 gene product expression that contributes to normal neuronal functions.
Full Text
Duke Authors
Cited Authors
- Mitsuda, N; Ohkubo, N; Tamatani, M; Lee, YD; Taniguchi, M; Namikawa, K; Kiyama, H; Yamaguchi, A; Sato, N; Sakata, K; Ogihara, T; Vitek, MP; Tohyama, M
Published Date
- March 30, 2001
Published In
Volume / Issue
- 276 / 13
Start / End Page
- 9688 - 9698
PubMed ID
- 11116137
International Standard Serial Number (ISSN)
- 0021-9258
Digital Object Identifier (DOI)
- 10.1074/jbc.M006153200
Language
- eng
Conference Location
- United States