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editorial

. 2019 Nov 20;11(2):82–84. doi: 10.1007/s13238-019-00673-x

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© The Author(s) 2019

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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A negative cascade of the FBXW2–MSX2–SOX2 axis is targeted by MLN4924. SOX2 (cicada) is a transcriptional downstream target of MSX2 (mantis). Upon binding to SOX2 gene promoter, MSX2 negatively controls SOX2 transcription. MSX2, on the other hand, is a substrate of FBXW2 (oriole) E3 ligase. Upon hypoxia, FBXW2 binds to MSX2 and targets it for ubiquitylation and subsequent degradation. By inactivating FBXW2, MLN4924 (man with a slingshot) causes MSX2 accumulation to transcriptionally repress SOX2