S100A8/S100A9 cytokine acts as a transcriptional coactivator during breast cellular transformation.
S100A8/S100A9 cytokine acts as a transcriptional coactivator during breast cellular transformation.
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DOI：
10.1126/sciadv.abe5357
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发表时间：
2021-01
期刊：
影响因子：
13.6
通讯作者：
Struhl K
中科院分区：
文献类型：
--
作者：
Song R;Struhl K
S100A8/S100A9是一种分泌型细胞因子，在细胞核中作为转录辅激活因子促进细胞转化。细胞因子是细胞外蛋白，通过与细胞表面同源受体相互作用，触发信号通路，以自分泌或旁分泌的方式改变基因表达和其他表型，在细胞间传递信息。本研究表明，在乳腺细胞转化模型中，钙依赖性细胞因子S100A8和S100A9被募集到众多启动子和增强子中。这种招募与DNA结合转录因子识别的多个DNA序列基序有关，这些DNA结合转录因子与转录激活有关，对转化很重要。细胞因子在核提取物中与这些转录因子相互作用，当人工招募到目标启动子时，它们会激活转录。S100A8/A9的核特异性表达促进致癌转录并导致乳腺转化表型增强。这些结果表明，除了其经典的细胞因子功能外，S100A8/A9还可以作为转录辅激活因子。
S100A8/S100A9, a secreted cytokine, also acts in the nucleus as a transcriptional coactivator to promote cellular transformation. Cytokines are extracellular proteins that convey messages between cells by interacting with cognate receptors at the cell surface and triggering signaling pathways that alter gene expression and other phenotypes in an autocrine or paracrine manner. Here, we show that the calcium-dependent cytokines S100A8 and S100A9 are recruited to numerous promoters and enhancers in a model of breast cellular transformation. This recruitment is associated with multiple DNA sequence motifs recognized by DNA binding transcription factors that are linked to transcriptional activation and are important for transformation. The cytokines interact with these transcription factors in nuclear extracts, and they activate transcription when artificially recruited to a target promoter. Nuclear-specific expression of S100A8/A9 promotes oncogenic transcription and leads to enhanced breast transformation phenotype. These results suggest that, in addition to its classical cytokine function, S100A8/A9 can act as a transcriptional coactivator.
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