New tumor suppressor CXXC finger protein 4 inactivates mitogen activated protein kinase signaling |
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| Authors: | Haiqi Lu Wei Jin Jie Sun Lifeng Feng Huiyin Lan Qi Shen Yanning Ma Jiaqiu Li Yongfang Yue Hongchuan Jin Xian Wang |
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| Institution: | 1. Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China;2. Laboratory of Cancer Biology, Institute of Clinical Science, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China |
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| Abstract: | 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/β-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. |
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| 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 |
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