CREB: a stimulus-induced transcription factor activated by a diverse array of extracellular signals

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Updated: Oct 15, 2026

Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells
09:16

Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells

Published on: September 1, 2019

A J Shaywitz1, M E Greenberg

  • 1Department of Neurology, Children's Hospital, Boston, Massachusetts, USA.

Annual Review of Biochemistry
|June 29, 2000
PubMed

Insights

Cyclic AMP response element (CRE)-binding protein (CREB) activates gene transcription via phosphorylation at serine 133. Different stimuli use distinct signaling pathways to regulate CREB, enabling specific gene expression programs.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Gene Regulation

Background:

  • Extracellular signals modulate gene expression through protein kinase cascades.
  • Cyclic AMP response element (CRE)-binding protein (CREB) is a key transcription factor activated by diverse stimuli.
  • Phosphorylation of CREB at serine 133 (Ser133) is crucial for its transcriptional activity.

Purpose of the Study:

  • To review the molecular mechanisms of Ser133-phosphorylated CREB transcriptional activation.
  • To explore intracellular signaling pathways leading to CREB phosphorylation at Ser133.
  • To understand how signaling pathways confer specificity to CREB activation.

Main Methods:

  • Literature review of molecular mechanisms.
  • Analysis of intracellular signaling pathways.
  • Examination of CREB phosphorylation and transcriptional regulation.

Main Results:

  • Multiple protein kinases (PKA, pp90RSK, CaMKs) phosphorylate CREB at Ser133.
  • Phosphorylation at Ser133 is essential for CREB-mediated transcription.
  • Stimulus-specific mechanisms, including additional phosphorylation sites or protein interactions, allow CREB to regulate distinct gene expression programs.

Conclusions:

  • CREB activation is a central node for integrating diverse extracellular signals.
  • Specificity in CREB-mediated gene regulation arises from stimulus-dependent signaling pathways.
  • Understanding CREB regulation provides insights into cellular responses to various stimuli.

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