Journal
FEBS LETTERS
Volume 588, Issue 18, Pages 3322-3326Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2014.07.014
Keywords
Enhancer of zeste homologue 2 (EZH2); CXXC finger protein 4 (CXXC4); Mitogen-activated protein kinase (MAPK); Extracellular signal-regulated kinase (ERK); MAP kinase (MEK); Gastric carcinogenesis
Funding
- Natural Science foundation of China [81071652, 81372178]
- Natural Science foundation of Zhejiang Province [LR12H16001]
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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.
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