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

作者:Juliana Farha M; Nara Hidetoshi; Onoda Tadashi; Rahman Mizanur; Araki Akemi; Jin Lianjin; Fujii Hodaka; Tanaka Nobuyuki; Hoshino Tomoaki; Asao Hironobu*
来源:Biochemical and Biophysical Research Communications, 2012, 420(3): 628-634.
DOI:10.1016/j.bbrc.2012.03.051

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 P13K 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.

  • 出版日期2012-4-13