Activated cAMP-response Element-binding Protein Regulates Neuronal Expression of Presenilin-1

Noriaki Mitsuda, Nobutaka Ohkubo, Michio Tamatani, Young Don Lee, Manabu Taniguchi, Kazuhiko Namikawa, Hiroshi Kiyama, Atsushi Yamaguchi, Naoyuki Sato, Kazuko Sakata, Toshio Ogihara, Michael P. Vitek, Masaya Tohyama

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)9688-9698
Number of pages11
JournalJournal of Biological Chemistry
Volume276
Issue number13
DOIs
StatePublished - Mar 30 2001

Fingerprint

Presenilin-1
Cyclic AMP Response Element-Binding Protein
Genes
Chemical activation
Mitogen-Activated Protein Kinase Kinases
Transcription
Brain-Derived Neurotrophic Factor
Nucleic Acid Databases
Extracellular Signal-Regulated MAP Kinases
Glutamate Receptors
Response Elements
N-Methylaspartate
Mitogen-Activated Protein Kinases
N-Methyl-D-Aspartate Receptors
Adenoviridae
Rats
Transcription Factors
Gene Expression

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Mitsuda, N., Ohkubo, N., Tamatani, M., Lee, Y. D., Taniguchi, M., Namikawa, K., ... Tohyama, M. (2001). Activated cAMP-response Element-binding Protein Regulates Neuronal Expression of Presenilin-1. Journal of Biological Chemistry, 276(13), 9688-9698. https://doi.org/10.1074/jbc.M006153200

Activated cAMP-response Element-binding Protein Regulates Neuronal Expression of Presenilin-1. / Mitsuda, Noriaki; Ohkubo, Nobutaka; Tamatani, Michio; Lee, Young Don; Taniguchi, Manabu; Namikawa, Kazuhiko; Kiyama, Hiroshi; Yamaguchi, Atsushi; Sato, Naoyuki; Sakata, Kazuko; Ogihara, Toshio; Vitek, Michael P.; Tohyama, Masaya.

In: Journal of Biological Chemistry, Vol. 276, No. 13, 30.03.2001, p. 9688-9698.

Research output: Contribution to journalArticle

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 2001, 'Activated cAMP-response Element-binding Protein Regulates Neuronal Expression of Presenilin-1', Journal of Biological Chemistry, vol. 276, no. 13, pp. 9688-9698. https://doi.org/10.1074/jbc.M006153200
Mitsuda, Noriaki ; Ohkubo, Nobutaka ; Tamatani, Michio ; Lee, Young Don ; Taniguchi, Manabu ; Namikawa, Kazuhiko ; Kiyama, Hiroshi ; Yamaguchi, Atsushi ; Sato, Naoyuki ; Sakata, Kazuko ; Ogihara, Toshio ; Vitek, Michael P. ; Tohyama, Masaya. / Activated cAMP-response Element-binding Protein Regulates Neuronal Expression of Presenilin-1. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 13. pp. 9688-9698.
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