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Title 

Mechanism of the natural product moracin-O derived MO-460 and its targeting protein hnRNPA2B1 on HIF-1α inhibition

Authors 

Nak Kyun SoungHye-Min KimY AsamiDong Hyun KimYangrae ChoR NaikY JangK JangH J HanS R GanipisettiHyunjoo ChaJoonsung HwangKyung Ho LeeSung-Kyun KoJae-Hyuk JangIn Ja RyooY T KwonK S LeeH OsadaK LeeBo Yeon KimJong Seog Ahn

Publisher 

Korean Society of Medical Biochemistry

Issue Date 

2019

Citation 

Experimental and Molecular Medicine

Abstract 

Hypoxia-inducible factor-1α (HIF-1α) mediates tumor cell adaptation to hypoxic conditions and is a potentially important anticancer therapeutic target. We previously developed a method for synthesizing a benzofuran-based natural product, (R)-(-)-moracin-O, and obtained a novel potent analog, MO-460 that suppresses the accumulation of HIF-1α in Hep3B cells. However, the molecular target and underlying mechanism of action of MO-460 remained unclear. In the current study, we identified heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) as a molecular target of MO-460. MO-460 inhibits the initiation of HIF-1α translation by binding to the C-terminal glycine-rich domain of hnRNPA2B1 and inhibiting its subsequent binding to the 3'-untranslated region of HIF-1α mRNA. Moreover, MO-460 suppresses HIF-1α protein synthesis under hypoxic conditions and induces the accumulation of stress granules. The data provided here suggest that hnRNPA2B1 serves as a crucial molecular target in hypoxia-induced tumor survival and thus offer an avenue for the development of novel anticancer therapies.

URI 

https://doi.org/10.1038/s12276-018-0200-4

ISSN 

1226-3613

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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