Lee, Jee Won Kang, Hye Seon Lee, Jae Youn Lee, Eun Jung Rhim, Hyewhon Yoon, Joo Heon Seo, Su Ryeon Chung, Kwang Chul 2024-01-20T15:02:26Z 2024-01-20T15:02:26Z 2021-09-05 2012-04-06 0006-291X https://pubs.kist.re.kr/handle/201004/129340 Down syndrome is the most common genetic disorder and is characterized by three copies of chromosome 21. Regulator of calcineurin 1 (RCAN1) is located close to the Down syndrome critical region (distal part of chromosome 21), and its product functions as an endogenous inhibitor of calcineurin signaling. RCAN1 protein stability is regulated by several inflammatory signaling factors, though the underlying mechanisms remain incompletely understood. Here, we report that RCAN1 interacts with the inflammation-linked transcription factor, signal transducer and activator of transcription 2 (STAT2) in mammalian cells. STAT2 overexpression decreased levels of RCAN1 protein. Decreases in RCAN1 were blocked by a proteasome inhibitor, indicating that STAT2 regulates RCAN1 degradation via the ubiquitin-proteasome system. Co-immunoprecipitation/immunoblot analyses showed that STAT2 enhanced RCAN1 ubiquitination through the ubiquitin E3 ligase FBW7. This pathway appeared to be physiologically relevant, as treatment of cells with interferon-alpha reduced RCAN1 levels through the activation of STAT2 and FBW7. Together, these results suggest that STAT2 influences diverse cellular processes linked to RCAN1 by negatively affecting RCAN1 protein stability. (C) 2012 Elsevier Inc. All rights reserved. English ACADEMIC PRESS INC ELSEVIER SCIENCE DOWN-SYNDROME INTERFERON-ALPHA CALCINEURIN DSCR1 PHOSPHORYLATION GENE CALCIPRESSIN-1 ACTIVATION INHIBITOR The transcription factor STAT2 enhances proteasomal degradation of RCAN1 through the ubiquitin E3 ligase FBW7 Article 10.1016/j.bbrc.2012.03.007 1 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.420, no.2, pp.404 - 410 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 420 2 404 410 scie scopus 000306042100033 2-s2.0-84862823681 Biochemistry & Molecular Biology Biophysics Biochemistry & Molecular Biology Biophysics Article DOWN-SYNDROME INTERFERON-ALPHA CALCINEURIN DSCR1 PHOSPHORYLATION GENE CALCIPRESSIN-1 ACTIVATION INHIBITOR RCAN1 DSCR1 STAT2 Proteasome FBW7 Inflammation Interferon-alpha