HDAC3 influences phosphorylation of STAT3 at serine 727 by interacting with PP2A.
HDAC3 influences phosphorylation of STAT3 at serine 727 by interacting with PP2A.
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DOI：
10.1016/j.bbrc.2008.12.132
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发表时间：
2009-02
影响因子：
3.1
通讯作者：
S. Togi;Shinya Kamitani;S. Kawakami;O. Ikeda;R. Muromoto;A. Nanbo;T. Matsuda
中科院分区：
文献类型：
--
作者：
S. Togi;Shinya Kamitani;S. Kawakami;O. Ikeda;R. Muromoto;A. Nanbo;T. Matsuda
信号转导子和转录激活子3（STAT 3）在许多生理过程中介导生物学作用，被细胞因子和生长因子激活，并已被报道参与多种人类疾病的发病机制。在这里，我们表明，治疗HeLa细胞与组蛋白脱乙酰酶（HDAC）抑制剂，抑制素A，或小干扰RNA（siRNA）介导的抑制HDAC 3，增强磷酸化的STAT 3在Ser 727。此外，通过用HDAC 3 siRNA处理细胞，蛋白磷酸酶2A（PP 2A）在Ser 727处对STAT 3的去磷酸化得以恢复。我们进一步发现，在HDAC 3存在下，STAT 3和PP 2A之间的复合物的形成增强。重要的是，小干扰RNA介导的HDAC 3和PP 2A的抑制有效地增强了白血病抑制因子（LIF）诱导的STAT 3激活。这些结果表明HDAC 3可能作为PP 2A的支架蛋白来调节LIF/STAT 3介导的信号通路。
Signal transducer and activator of transcription 3 (STAT3), which mediates biological actions in many physiological processes, is activated by cytokines and growth factors, and has been reported to be involved in the pathogenesis of various human diseases. Here, we show that treatment of HeLa cells with a histone deacetylase (HDAC) inhibitor, trichostatin A, or small-interfering RNA (siRNA)-mediated repression of HDAC3, enhances phosphorylation of STAT3 at Ser727. Furthermore, dephosphorylation of STAT3 at Ser727 by protein phosphatase 2A (PP2A) was restored by treatment of cells with HDAC3 siRNA. We further found that formation of a complex between STAT3 and PP2A was enhanced in the presence of HDAC3. Importantly, small-interfering RNA-mediated repression of both HDAC3 and PP2A effectively enhanced leukemia inhibitory factor (LIF)-induced STAT3 activation. These results indicate that HDAC3 may act as a scaffold protein for PP2A to regulate the LIF/STAT3-mediated signaling pathway.