The transcription factor STAT2 enhances proteasomal degradation of RCAN1 through the ubiquitin E3 ligase FBW7
- The transcription factor STAT2 enhances proteasomal degradation of RCAN1 through the ubiquitin E3 ligase FBW7
- 이지원; 강혜선; 이재윤; 이은정; 임혜원; 윤주현; 서수련; 정광철
- RCAN1; DSCR1; STAT2; Proteasome; FBW7; Inflammation; Interferon-α
- Issue Date
- Biochemical and biophysical research communications
- VOL 420, NO 2, 404-410
- 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.
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