Regulation of HIF1α expression by a natural compound; a new hnRNP involvement
Bo Yeon Kim1
,Yukihiro Asami1
, Nak Kyun Soung1
, Hae Min Kim1
, Jae Hyuk Jang1
, N.R. Themmegowda1
, Jong Seog Ahn1 and Kyung Lee2
1
Korea Research Institute of Bioscience & Biotechnology, Korea 2
Department of Pharmacology, DongKook University, Korea
Hypoxia induces HIF1aexpression, leading to the malignant cell transformation. In screening of inhibitors against HIF1aexpression
using a reporter gene assay system, a moracin derivative, MOA, was found to strongly reduce the level of HIF1ain HeLa
cellsboth in hypoxia-mimetic CoCl2
treatment and under hypoxic conditions. Identification of binding proteins using agarose-bead
conjugated MOA(AC-685) combined with subsequent MS data revealed several proteins affected by MOA. AC-685 co-localized
with a nuclear hnRNPX protein in CoCl2
 treated HeLa cells. Amongst several cytoplasmic or nuclear proteins, hnRNPX was only
found to be responsible for CoCl2
-induced HIF1α expression as supported by siRNA depletion of the protein. Cancer growth was
also found to be reduced in a genograft animal model. This study suggests that regulation of HIF1aexpression by MOAunder the
control of hnRNP would be a novel approach to cancer treatment in hypoxic environment.
Biography:
Dr. Bo Yeon Kim got Ph.D degree at Seoul National University in 1996. After the research fellow experience at Georgetown University, 2000-2003,
he continued his work at Korea Research Institute of Bioscience & Biotechnology (KRIBB) for about 26 yrs so far. Major research focuses on
identification of new cancer signaling pathways and development of a new anticancer drug with low side effect. In recent 5 years, He has made more
than 65 publications, including Nature Cell Biology (2015), Autophagy (2016, 2013), Proc Natl Acad Sci, USA (2013), J Am Chem Soc (2011), J Biol
Chem (2013, 2012), and under revision papers (Nature Communicaitons, EMBO Reports, Autophagy) as a corresponding author.