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http://dx.doi.org/10.5352/JLS.2013.23.10.1183

APEX-1 Regulates Cell Proliferation through GDNF/GFRα1 Signaling  

Kim, Hong-Beum (Department of Bio-materials, Chosun University)
Hariharasudhan, Gurusamy (Department of Bio-materials, Chosun University)
Youn, Cha-Kyung (Department of Bio-materials, Chosun University)
Publication Information
Journal of Life Science / v.23, no.10, 2013 , pp. 1183-1191 More about this Journal
Abstract
Human apurinic/apyrimidinic endonuclease (APEX-1) is a multifunctional protein that is capable of repairing abasic sites and single-strand breaks in damaged DNA. In addition, it serves as a redox-modifying factor for a number of transcription factors. Identifying the transcriptional targets of APEX-1 is essential for understanding how it affects various cellular outcomes. Expression array analysis was used to identify glial cell-derived neurotropic factor receptor ${\alpha}1$ ($GFR{\alpha}1$), which is an encoding receptor for the glial cell-derived neurotropic factor (GDNF) family, the expression of which is induced by APEX-1. A target of GDNF/$GFR{\alpha}$ signaling, c-Src (Tyr418) was strongly phosphorylated by GNDF in the APEX-1 expressing cells. Moreover, GDNF initiated cell proliferation, measured by counting the number of cells, in the APEX-1 expressing cells. Importantly, the down-regulation of APEX-1 by siRNA caused a marked reduction in the $GFR{\alpha}1$ expression level, and it reduced the ability of GDNF to phosphorylate c-Src (Tyr418) and stimulate cell proliferation. These results demonstrate an association between APEX-1 and GDNF/$GFR{\alpha}$ signaling and suggest a potential molecular mechanism for the involvement of APEX-1 in cell survival and proliferation.
Keywords
Apurinic/apyrimidinic endonuclease (APEX-1); cell proliferation; glial cell-derived neurotropic factor (GDNF); glial cell-derived neurotropic factor receptor ${\alpha}1$ ($GFR{\alpha}1$); Src;
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