DNA damage induced apoptosis suppressor (DDIAS) is upregulated via ERK5/MEF2B signaling and promotes β-catenin-mediated invasion = ERK5/MEF2B 신호전달을 통한 DDIAS의 발현 증가 및 β-catenin 의 invasion 촉진

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Title
DNA damage induced apoptosis suppressor (DDIAS) is upregulated via ERK5/MEF2B signaling and promotes β-catenin-mediated invasion = ERK5/MEF2B 신호전달을 통한 DDIAS의 발현 증가 및 β-catenin 의 invasion 촉진
Author(s)
Joo-Young Im; Sung Hoon Yoon; Bo Kyung KimHyun Seung Ban; Kyoung-Jae Won; Kyung-Sook Chung; K E Jung; Mi Sun Won
Bibliographic Citation
Biochimica et Biophysica Acta-Gene Regulatory Mechanisms, vol. 1859, pp. 1449-1458
Publication Year
2016
Abstract
DNA damage induced apoptosis suppressor (DDIAS) is an anti-apoptotic protein that promotes cancer cell survival. We previously reported that DDIAS is transcriptionally activated by nuclear factor of activated T cells 2 (NFATc1). However, the upstream regulation of DDIAS expression by growth factors has not been studied. Here, we demonstrate that DDIAS expression is induced by extracellular signal-regulated kinase 5 (ERK5) and myocyte enhancer factor 2B (MEF2B) in response to epidermal growth factor (EGF) and that it positively regulates β-catenin signaling in HeLa cells. The genetic or pharmacological inhibition of ERK5 suppressed DDIAS induction following EGF exposure and the overexpression of constitutively active MEK5 (CA-MEK5) enhanced DDIAS expression. In chromatin immunoprecipitation assays, MEF2B, a downstream target of ERK5, exhibited sequence-specific binding to a MEF2 binding site in the DDIAS promoter following treatment with EGF. The overexpression of MEF2B increased the EGF-mediated induction of DDIAS expression, whereas the knockdown of MEF2B impaired this effect. Furthermore, DDIAS promoted invasion by increasing β-catenin expression at the post-translational level in response to EGF, suggesting that DDIAS plays a crucial role in the metastasis of cancer cells by regulating β-catenin expression. It is unlikely that MEF2B and NFATc1 cooperatively regulate DDIAS transcription in response to EGF. Collectively, EGF activates the ERK5/MEF2 pathway, which in turn induces DDIAS expression to promote cancer cell invasion by activating β-catenin target genes.
Keyword
DDIASEGFERK5InvasionMEF2Bβ-catenin
ISSN
1874-9399
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.bbagrm.2016.07.003
Type
Article
Appears in Collections:
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
Division of Biomedical Research > Biotherapeutics Translational Research Center > 1. Journal Articles
Division of Research on National Challenges > 1. Journal Articles
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