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.
Bibliographical noteFunding Information:
This work was supported by the Korea Research Foundation Grant funded from the Korean Government (KRF-2006-331-C00239, and KRF-2004-005-E00017), 2007 Research Grant from Kangwon National University, and by the Brain Korea 21 program to S.R.S. This study was also funded by Grants from the Brain Research Center of the 21st Century Frontier Research Program Technology (M103KV010011-06K2201-01110), KOSEF (R11-2007-040-01005-0, R04-2007-000-20014-0, and R01-2007-000-20089-0), and the Korea Health 21 R&D Project (A060440) to K.C.C. This work originated at Yonsei University and was carried out in facilities of the Institute of Bioscience and Biotechnology at Kangwon National University.
All Science Journal Classification (ASJC) codes
- Structural Biology
- Molecular Biology
- Cell Biology