Nuclear protein I{kappa}B-{zeta} inhibits the activity of STAT3
- State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850 (China)
- Department of Biological Sciences and Biotechnology, Institute of Biomedicine, Tsinghua University, Beijing 100084 (China)
STAT3 (Signal transducer and activator of transcription 3) is a key transcription factor of the JAK-STAT (Janus kinase/signal transducer and activator of transcription) pathway that regulates cell proliferation and apoptosis. Activation of STAT3 is under tight regulation, and yet the different signaling pathways and the mechanisms that regulate its activity remain to be elucidated. Using a yeast two-hybrid screening, we have identified a nuclear protein I{kappa}B-{zeta} that interacts in a novel way with STAT3. This physical interaction was further confirmed by co-immunoprecipitation assays. The interaction regions were mapped to the coiled-coil domain of STAT3 and the C-terminal of I{kappa}B-{zeta}. Overexpression of I{kappa}B-{zeta} inhibited the transcriptional activity of STAT3. It also suppressed cell growth and induced cell apoptosis in SRC-simulated cells, which is partially mediated by down-regulation of expression of a known STAT3 target gene, MCL1. Our results suggest that I{kappa}B-{zeta} is a negative regulator of STAT3, and demonstrate a novel mechanism in which a component of the NF-{kappa}B signaling pathway inhibits the activation of STAT3.
- OSTI ID:
- 22199801
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 387; ISSN 0006-291X; ISSN BBRCA9
- Country of Publication:
- United States
- Language:
- English
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