CREB activates proteasomal degradation of DSCR1/RCAN1.
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.
Seo
Su Ryeon
SR
Department of Molecular Bioscience, School of Bioscience and Biotechnology, Kangwon National University, Chuncheon 200-701, Republic of Korea. suryeonseo@kangwon.ac.kr <suryeonseo@kangwon.ac.kr>
Chung
Kwang Chul
KC
D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004268:DNA-Binding Proteins; D004314:Down Syndrome / Q000201:enzymology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors; D015533:Transcriptional Activation; D054875:Ubiquitination
C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D015853:Cysteine Proteinase Inhibitors; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D061988:Proteasome Inhibitors; C108612:RCAN1 protein, human; D046988:Proteasome Endopeptidase Complex