期刊
FEBS LETTERS
卷 582, 期 13, 页码 1889-1893出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2008.04.059
关键词
CREB; DSCR1/RCAN1; ubiquitin-proteasome; DS
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. (c) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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