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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

Authors 

Joo-Young ImSung Hoon YoonBo Kyung KimHyun Seung BanKyoung-Jae WonKyung-Sook ChungK E JungMi Sun Won

Publisher 

Elsevier

Issue Date 

2016

Citation 

BBA - Gene Regulatory Mechanisms, vol. 1859, no. 0, pp. 1449-1458

Keywords 

DDIASEGFERK5InvasionMEF2Bβ-catenin

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.

ISSN 

1874-9399

Link 

http://dx.doi.org/10.1016/j.bbagrm.2016.07.003

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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