A new mechanism of SOX9 action to regulate PKCα expression in the intestine epithelium
A new mechanism of SOX9 action to regulate PKCα expression in the intestine epithelium
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DOI：
10.1242/jcs.036483
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发表时间：
2009-07-01
影响因子：
4
通讯作者：
Quittau-Prevostel, Corinne
中科院分区：
文献类型：
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作者：
Dupasquier, Sebastien;Abdel-Samad, Rana;Quittau-Prevostel, Corinne
蛋白激酶C（PKC）表达的变化对肠上皮细胞的增殖分化转化（PDT）有重要影响，可能对肠肿瘤的发生有重要影响。我们在这里证明，PKC α的表达在增殖的肠上皮细胞被抑制在体外和体内的SOX 9转录因子。这种抑制不需要DNA结合的SOX 9高迁移率族（HMG）结构域，但通过一种新的机制介导的SOX 9的行动，需要中央和高度保守的区域SOXE成员。由于SOX 9表达本身在肠上皮细胞中被Wnt-APC信号上调，本研究指出该转录因子是Wnt-APC通路和PKCa之间的分子联系。这些结果为结直肠癌中PKCa表达的减少和Wnt-APC通路的组成性激活提供了潜在的解释。
Variations of protein kinase C (PKC) expression greatly influence the proliferation-to-differentiation transition (PDT) of intestinal epithelial cells and might have an important impact on intestinal tumorigenesis. We demonstrate here that the expression of PKC alpha in proliferating intestinal epithelial cells is repressed both in vitro and in vivo by the SOX9 transcription factor. This repression does not require DNA binding of the SOX9 high-mobility group (HMG) domain but is mediated through a new mechanism of SOX9 action requiring the central and highly conserved region of SOXE members. Because SOX9 expression is itself upregulated by Wnt-APC signaling in intestinal epithelial cells, the present study points out this transcription factor as a molecular link between the Wnt-APC pathway and PKCa. These results provide a potential explanation for the decrease of PKCa expression in colorectal cancers with constitutive activation of the Wnt-APC pathway.