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-α 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.
|Number of pages||7|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - 2012 Apr 6|
Bibliographical noteFunding Information:
This study was supported by grants from the Korea Healthcare technology R&D Project (A092004 and A111653 to K.C.C.) funded by Ministry for Health, Welfare & Family Affairs, Republic of Korea. This work was also partially supported by grants from the Brain Research Center of the 21st Century Frontier Research Program Technology (2009K-001251 to K.C.C.), the National Research Foundation of Korea (NRF) (2010-0018916 to K.C.C.), and the Basic Science Research Program through NRF (2012-0000810 to K.C.C.) all funded by the Ministry of Education, Science and Technology (MEST), Republic of Korea.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology