Physical and functional interactions between STAT3 and KAP1
Physical and functional interactions between STAT3 and KAP1
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DOI：
10.1038/sj.onc.1210952
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发表时间：
2008-05-08
期刊：
影响因子：
8
通讯作者：
Matsuda, T.
中科院分区：
文献类型：
--
作者：
Tsuruma, R.;Ohbayashi, N.;Matsuda, T.
信号转导和转录激活因子(STATs)在免疫反应、造血、神经发生和其他生物过程中介导细胞的增殖、分化和存活。例如，据报道，STAT3在许多癌细胞中被结构性激活。为了阐明STAT激活的分子机制，我们进行了酵母双杂交筛选，确定KAP1/TIF1b是一个新的STAT结合伙伴。KAP1是Kruppel相关盒锌指蛋白超家族转录抑制因子的通用辅阻遏子蛋白。我们在体内发现内源性KAP1与内源性STAT3相关。重要的是，小干扰RNA介导的KAP1表达的降低增强了IL-6诱导的STAT3依赖的转录和基因表达。此外，KAP1表达的降低导致Ser727上的STAT3磷酸化在细胞核内显著积聚。调节其转录激活的阳离子。这些结果表明，KAP1可能是IL-6/STAT3信号通路的转录调节因子。
Signal transducers and activators of transcription (STATs) mediate cell proliferation, differentiation and survival in immune responses, hematopoiesis, neurogenesis and other biological processes. For example, STAT3 has been reported to be constitutively activated in numerous cancer cells. To clarify the molecular mechanisms underlying the STAT activation, we performed yeast two-hybrid screening and identified KAP1/TIF1b as a novel STAT-binding partner. KAP1 is a universal corepressor protein for the Kruppel-associated box zinc-finger protein superfamily of transcriptional repressors. We found endogenous KAP1 associated with endogenous STAT3 in vivo. Importantly, small-interfering RNA-mediated reduction of KAP1 expression enhanced interleukin (IL)-6-induced STAT3-dependent transcription and gene expression. Furthermore, reduction of KAP1 expression resulted in the marked accumulation of STAT3 phosphorylated on Ser727 in the nucleus, a modi. cation that regulates its transcriptional activation. These results indicate that KAP1 may serve as a transcriptional regulator of the IL-6/STAT3 signaling pathway.