Up-regulation of cyclin D1 by HBx is mediated by NF-κB2/BCL3 complex through κB site of cyclin D1 promoter
Up-regulation of cyclin D1 by HBx is mediated by NF-κB2/BCL3 complex through κB site of cyclin D1 promoter
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DOI：
10.1074/jbc.m603194200
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发表时间：
2006-10-20
影响因子：
4.8
通讯作者：
Jung, Guhung
中科院分区：
文献类型：
--
作者：
Park, Sung Gyoo;Chung, Chan;Jung, Guhung
细胞周期蛋白D1在肝细胞癌（HCC）中经常过度表达，表现出增加的恶性表型。我们也知道乙肝（HBx）蛋白与HCC的发生和进展密切相关。虽然这两种蛋白的过表达与HCC有关，但两者之间的关系尚未得到很好的研究。本研究表明，HBx上调cyclin D1，这一过程是由NF-kappa B2(p52)/BCL-3复合物介导的。我们的实验表明，HBx在mRNA水平上上调BCL-3，从而导致细胞核中NF-kappa B2(p52)/BCL-3复合物的上调。此外，hbx介导的BCL-3上调被BCL-3的小干扰RNA破坏，降低了hbx介导的cyclin D1上调。p53下调HBx蛋白水平也降低了HBx介导的cyclin D1上调。根据这些结果，我们认为HBx上调细胞周期蛋白D1是通过上调细胞核内NF-kappa B2(p52)/BCL-3介导的。这种由hbx介导的细胞周期蛋白D1上调可能在hbx介导的HCC发生和进展中起重要作用。
Cyclin D1 is frequently overexpressed in hepatocellular carcinoma (HCC) exhibiting increased malignant phenotypes. It has also been known that the hepatitis Bx (HBx) protein is strongly associated with HCC development and progression. Although overexpression of both proteins is related to HCC, the relationship between the two has not been well studied. Here we show that HBx up-regulates cyclin D1 and that this process is mediated by the NF-kappa B2(p52)/BCL-3 complex. Our experiments indicate that HBx up-regulates BCL-3 in the mRNA level, which subsequently results in the up-regulation of the NF-kappa B2(p52)/BCL-3 complex in the nucleus. Moreover, impaired HBx-mediated BCL-3 up-regulation by small interfering RNA for BCL-3 reduced HBx-mediated cyclin D1 up-regulation. Down-regulation of the HBx protein level by p53 also reduced HBx-mediated cyclin D1 up-regulation. From these results, we conclude that the up-regulation of cyclin D1 by HBx is mediated by the up-regulation of NF-kappa B2(p52)/BCL-3 in the nucleus. This HBx-mediated cyclin D1 up-regulation might play an important role in the HBx-mediated HCC development and progression.