Nuclear protein IκB-ζ inhibits the activity of STAT3

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• 作者：Zhihao Wu ; Xiaoai Zhang ; Juntao Yang ; Guangzhou Wu ; Ying Zhang ; Yanzhi Yuan ; Chaozhi Jin ; Zhijie Chang ; Jian Wang ; Xiaoming Yang ; Fuchu He
• 关键词：Iκ ; B-ζ ; STAT3 ; Inhibition ; Transcription ; Apoptosis
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2009
• 出版时间：18 September 2009
• 年：2009
• 卷：387
• 期：2
• 页码：348-352
• 全文大小：634 K

文摘

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 IκB-ζ 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 IκB-ζ. Overexpression of IκB-ζ 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 IκB-ζ is a negative regulator of STAT3, and demonstrate a novel mechanism in which a component of the NF-κB signaling pathway inhibits the activation of STAT3.