New tumor suppressor CXXC finger protein 4 inactivates mitogen activated protein kinase signaling
New tumor suppressor CXXC finger protein 4 inactivates mitogen activated protein kinase signaling
复制标题
新肿瘤抑制因子 CXXC 指蛋白 4 使丝裂原激活蛋白激酶信号失活
DOI：
10.1016/j.febslet.2014.07.014
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发表时间：
2014-09-17
期刊：
影响因子：
3.5
通讯作者：
Wang, Xian
中科院分区：
文献类型：
--
作者：
Lu, Haiqi;Jin, Wei;Wang, Xian
EZH2作为表观遗传调控网络中的主要参与者，广泛参与许多恶性肿瘤的发展。我们先前发现EZH2通过下调CXXC4表达促进Wnt/β-连环蛋白激活。在本报告中，我们证明了CXXC4通过与ERK-1/2结合并消除ERK 1/2与MEK 1/2的相互作用来抑制MAPK信号传导。CXXC4 ERK D结构域的关键残基L183是CXXC4与ERK 1/2相互作用和CXXC4抑制肿瘤细胞生长的关键残基。总之，CXXC4直接破坏MEK 1/2-ERK 1/2相互作用以抑制MAPK信号传导。L183位点是CXXC4与ERK 1/2结合及CXXC4的生长抑制作用所必需的。因此，EZH2可以通过抑制CXXC4表达来激活MAPK信号传导。(C)2014年欧洲生物化学学会联合会。Elsevier B.V.出版，保留所有权利。
As a well-characterized master player in epigenetic regulatory network, EZH2 is widely implicated in the development of many malignancies. We previously found that EZH2 promoted Wnt/beta-catenin activation through downregulation of CXXC4 expression. In this report, we demonstrated that CXXC4 inhibited MAPK signaling through binding to ERK-1/2 and abrogating the interaction of ERK 1/2 with MEK1/2. L183, the critical residue in CXXC4 ERK D domain, was found to be essential for CXXC4-ERK 1/2 interaction and the growth inhibitory effect of CXXC4 in human cancer cells. In summary, CXXC4 directly disrupted MEK1/2-ERK 1/2 interaction to inactivate MAPK signaling. L183 site is indispensable for the binding of CXXC4 to ERK1/2 and growth inhibitory effect of CXXC4. Therefore, EZH2 can activate MAPK signaling by inhibiting CXXC4 expression. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.