CREB activates proteasomal degradation of DSCR1/RCAN1

FEBS Lett. 2008 Jun 11;582(13):1889-93. doi: 10.1016/j.febslet.2008.04.059. Epub 2008 May 15.

Abstract

The cyclic AMP response element-binding protein (CREB) is involved in the development and function of the nervous system. Here, we find that CREB decreases the protein level of Regulator of Calcineurin Activity 1 (RCAN1/DSCR1/MCIP1), which is overexpressed in the brain of Down Syndrome (DS) patients. Decrease of RCAN1 by CREB was blocked by proteasome inhibitors, indicating that this decrease is mediated by the ubiquitin-proteasome pathway. Furthermore, we found that the ability of CREB to activate the degradation of RCAN1 depends on its transcriptional activation. Consistently, CREB-enhanced the ubiquitination and turnover rate of RCAN1. Our results reveal a new regulatory role for CREB in DS pathology through the proteasomal degradation of RCAN1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Cysteine Proteinase Inhibitors / pharmacology
  • DNA-Binding Proteins
  • Down Syndrome / enzymology
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Neurons / metabolism*
  • Proteasome Endopeptidase Complex / metabolism*
  • Proteasome Inhibitors
  • Transcriptional Activation*
  • Ubiquitination*

Substances

  • CREB1 protein, human
  • Cyclic AMP Response Element-Binding Protein
  • Cysteine Proteinase Inhibitors
  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • Muscle Proteins
  • Proteasome Inhibitors
  • RCAN1 protein, human
  • Proteasome Endopeptidase Complex