The transcription factor STAT2 enhances proteasomal degradation of RCAN1 through the ubiquitin E3 ligase FBW7

Jee Won Lee, Hye Seon Kang, Jae Youn Lee, Eun Jung Lee, Hyewhon Rhim, Joo Heon Yoon, Su Ryeon Seo, Kwang Chul Chung

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)404-410
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume420
Issue number2
DOIs
Publication statusPublished - 2012 Apr 6

Fingerprint

STAT2 Transcription Factor
Ubiquitin-Protein Ligases
Calcineurin
Transcription Factors
Degradation
Chromosomes, Human, Pair 21
Protein Stability
Chromosomes
Cells
Inborn Genetic Diseases
Proteins
Proteasome Inhibitors
Ubiquitination
Proteasome Endopeptidase Complex
Ubiquitin
Down Syndrome
Immunoprecipitation
Interferons

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Lee, Jee Won ; Kang, Hye Seon ; Lee, Jae Youn ; Lee, Eun Jung ; Rhim, Hyewhon ; Yoon, Joo Heon ; Seo, Su Ryeon ; Chung, Kwang Chul. / The transcription factor STAT2 enhances proteasomal degradation of RCAN1 through the ubiquitin E3 ligase FBW7. In: Biochemical and Biophysical Research Communications. 2012 ; Vol. 420, No. 2. pp. 404-410.
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The transcription factor STAT2 enhances proteasomal degradation of RCAN1 through the ubiquitin E3 ligase FBW7. / Lee, Jee Won; Kang, Hye Seon; Lee, Jae Youn; Lee, Eun Jung; Rhim, Hyewhon; Yoon, Joo Heon; Seo, Su Ryeon; Chung, Kwang Chul.

In: Biochemical and Biophysical Research Communications, Vol. 420, No. 2, 06.04.2012, p. 404-410.

Research output: Contribution to journalArticle

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