The study of the protective effect of APE

Abstract

Human apurinic/apyrimidinic endonuclease (APE) 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 APE is essential for understanding the mechanisms for how it affects various cellular outcomes. Expression array analysis was used to identify glial cell-derived neurotropic factor receptor ??1 (GFR??1), which is an encoding receptor for the glial cell-derived neurotropic factor (GDNF) family, whose expression was induced by APE. Activation of NF-??B following APE expression represents a possible mechanism of APE-induced GFR??1 expression. Tumor progression of pancreatic cancers critically depends on activation of GDNF/ GFR??1 signal pathway. Our results indicate that APE-mediated increase in GFR??1 contributes to pancreatic tumor proliferation and invasion. The relationship with GFR??1 suggests that APE is also directly linked to regulation of neuron cell proliferation and survival, which may be important for promoting stress resistance and regulating life span under normal conditions. Thus, APE-mediated increase in GFR??1 may be a potential therapeutic target for neurodegenerative disorder. These studies indicate that understanding the relationship of APE to activation of GDNF responsiveness may reveal new insights into the important role of APE, such as cancer progression and neuron cell survival