Upregulation of annexin A1 expression by butyrate in human colon adenocarcinoma cells: Role of p53, NF-Y, and p38 mitogen-activated protein kinase
Upregulation of annexin A1 expression by butyrate in human colon adenocarcinoma cells: Role of p53, NF-Y, and p38 mitogen-activated protein kinase
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DOI：
10.1128/mcb.00650-07
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发表时间：
2008-08-01
影响因子：
5.3
通讯作者：
Lizarbe, M. A.
中科院分区：
文献类型：
--
作者：
Lecona, E.;Barrasa, J. I.;Lizarbe, M. A.
膜联蛋白 A1 是磷脂和钙结合蛋白家族的成员；它参与抗炎以及分化、增殖和凋亡的调节。在这里，我们展示了近端 CCAAT 盒附近存在肿瘤抑制因子 p53 的功能性结合位点，以及人结肠腺癌细胞中膜联蛋白 A1 的基础表达在转录水平上由 p53 驱动的事实。转录后机制也可能在维持膜联蛋白 A1 的组成型表达中发挥重要作用。此外，检测到 p53/NF-Y 复合物与其启动子上的 p53 结合位点结合。丁酸盐是结肠中纤维降解的天然产物，也是结肠上皮稳态的关键调节剂。我们发现丁酸盐是一种 I 类和 11 组蛋白脱乙酰酶抑制剂，可诱导与分化相关的膜联蛋白 A1 表达的转录激活。丁酸盐的作用是通过近端 CCAAT 盒释放 NF-Y 和增强 p53 结合来介导的。 p53 与启动子的相互作用取决于 p38 MAPK 活性，无论丁酸盐存在还是不存在。此外，该试剂激活 p38 MAPK 是增加膜联蛋白 A1 启动子活性和增加蛋白质表达所必需的。
Annexin A1 is a member of a phospholipid and calcium binding family of proteins; it is involved in anti-inflammation and in the regulation of differentiation, proliferation, and apoptosis. Here, we show the existence of a functional binding site for the tumor suppressor p53 near the proximal CCAAT box and the fact that the basal expression of annexin A1 in human colon adenocarcinoma cells is driven by p53 at the transcriptional level. Posttranscriptional mechanisms may also play an important role in maintaining constitutive annexin A1 expression. In addition, a p53/NF-Y complex is detected bound to the p53 binding site on its promoter. Butyrate is a natural product of fiber degradation in the colon and a key regulator of colonic epithelium homeostasis. We show that butyrate, a class I and 11 histone deacetylase inhibitor, induces transcriptional activation of annexin A1 expression correlated with differentiation. The effect of butyrate is mediated through a release of NF-Y from the proximal CCAAT box and an enhancement of p53 binding. The interaction of p53 with the promoter is dependent on p38 MAPK activity either in the absence or in the presence of butyrate. Further, activation of p38 MAPK by this agent is required to increase annexin A1 promoter activity and to increase protein expression.