Apurinic/apyrimidinic endonuclease1/redox factor-1 (Ape1/Ref-1) is essential for IL-21-induced signal transduction through ERK1/2 pathway

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• 作者：Farha M. Juliana^a ; Hidetoshi Nara^a ; Tadashi Onoda^a ; ^b ; Mizanur Rahman^a ; Akemi Araki^a ; Lianjin Jin^a ; Hodaka Fujii^c ; Nobuyuki Tanaka^d ; ^e ; Tomoaki Hoshino^f ; Hironobu Asao^a ; ^{asao-h@med.id.yamagata-u.ac.jp}
• 关键词：Ape1/Ref-1 ; apurinic/apyrimidinic endonuclease 1/redox effector factor-1 ; ROS ; reactive oxygen species ; Dox ; doxycycline
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 期刊代码：159_0006291x
• 类别：bio
• 出版时间：13 April, 2012
• 卷：420
• 期：3
• 页码：628-634
• 文件大小：743 K

摘要

IL-21 is a pleiotropic cytokine that regulates T-cell and B-cell differentiation, NK-cell activation, and dendritic cell functions. IL-21 activates the JAK-STAT, ERK, and PI3K pathways. We report here that Ape1/Ref-1 has an essential role in IL-21-induced cell growth signal transduction. Overexpression of Ape1/Ref-1 enhances IL-21-induced cell proliferation, but it is suppressed by overexpressing an N-terminal deletion mutant of Ape1/Ref-1 that lacks the redox domain. Furthermore, knockdown of the Ape1/Ref-1 mRNA dramatically compromises IL-21-induced ERK1/2 activation and cell proliferation with increasing cell death. These impaired activities are recovered by the re-expression of Ape1/Ref-1 in the knockdown cells. Our findings are the first demonstration that Ape1/Ref-1 is an indispensable molecule for the IL-21-mediated signal transduction through ERK1/2 activation.