Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Scienze Biochimiche, Università 'La Sapienza', Rome, Italy.
Arch Biochem Biophys. 2010 Feb 15;494(2):178-83. doi: 10.1016/j.abb.2009.12.004. Epub 2009 Dec 6.
Chromatin immunoprecipitation in M14 melanoma cells showed that the protein ERp57 (endoplasmic reticulum protein 57) binds to DNA in the proximity of STAT3 in a subset of STAT3-regulated genes. In the same cells, IL-6 induced a significant increase of the expression of one of these genes, i.e. CRP. Upon depletion of ERp57 by RNA interference, the phosphorylation of STAT3 on tyrosine 705 was decreased, and the IL-6-induced activation of CRP expression was completely suppressed. In vitro experiments showed that ERp57 is also required for the binding of STAT3 to its consensus sequence on DNA. Thus ERp57, previously shown to associate with STAT3 in the cytosol and in the nuclear STAT3-containing enhanceosome, is a necessary cofactor for the regulation of at least a subset of STAT3-dependent genes, probably intervening both at the site of STAT3 phosphorylation and at the nuclear level.
在 M14 黑色素瘤细胞中的染色质免疫沉淀实验表明，内质网蛋白 57（ERp57）与 STAT3 调节的基因中一组 STAT3 附近的 DNA 结合。在相同的细胞中，IL-6 诱导这些基因之一，即 CRP 的表达显著增加。通过 RNA 干扰耗尽 ERp57 后，STAT3 酪氨酸 705 的磷酸化减少，并且 IL-6 诱导的 CRP 表达的激活被完全抑制。体外实验表明，ERp57 对于 STAT3 与其 DNA 上的共有序列结合也是必需的。因此，先前已经显示 ERp57 与细胞质中的 STAT3 和包含核 STAT3 的增强子复合物相关联，是至少一部分 STAT3 依赖性基因调节的必要辅助因子，可能在 STAT3 磷酸化部位和核水平上均发挥作用。
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