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CREB activates proteasomal degradation of DSCR1/RCAN1
Author(s) -
Seo Su Ryeon,
Chung Kwang Chul
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.04.059
Subject(s) - creb , proteasome , ubiquitin , regulator , microbiology and biotechnology , cyclic amp response element binding protein , chemistry , calcineurin , biology , transcription factor , medicine , biochemistry , gene , transplantation
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.