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KMID : 0613820130230101183
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Journal of Life Science
2013 Volume.23 No. 10 p.1183 ~ p.1191
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APEX-1 Regulates Cell Proliferation through GDNF/GFRα1 Signaling
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Kim Hong-Beum
Hariharasudhan Gurusamy
Youn Cha-Kyung
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Abstract
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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 α1 (GFRα1), 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/GFRα1 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 GFRα1 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/GFRα1 signaling and suggest a potential molecular mechanism for the involvement of APEX-1 in cell survival and proliferation.
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KEYWORD
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Apurinic/apyrimidinic endonuclease (APEX-1), cell proliferation, glial cell-derived neurotropic factor (GDNF), glial cell-derived neurotropic factor receptor α1 (GFRα1), Src
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