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

Journal Article · Fri Apr 13 00:00:00 EDT 2012 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2012.03.051· OSTI ID:22207807

Juliana, Farha M.; Nara, Hidetoshi ^[1]; Onoda, Tadashi ^[1]; Rahman, Mizanur; Araki, Akemi; Jin, Lianjin ^[1]; Fujii, Hodaka ^[2]; Tanaka, Nobuyuki ^[3]; Hoshino, Tomoaki ^[4]; Asao, Hironobu ^[1]

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1. Department of Immunology, Yamagata University Faculty of Medicine, Yamagata (Japan)
2. Combined Program on Microbiology and Immunology, Research Institute for Microbial Diseases, Osaka University, Suita (Japan)
3. Division of Immunology, Miyagi Cancer Center Research Institute, Natori (Japan)
4. Department of Internal Medicine 1, Kurume University School of Medicine, Kurume (Japan)

Highlights: Black-Right-Pointing-Pointer IL-21 induces nuclear accumulation of Ape1/Ref-1 protein. Black-Right-Pointing-Pointer Ape1/Ref-1 is indispensable in IL-21-induced cell proliferation and survival signal. Black-Right-Pointing-Pointer Ape1/Ref-1 is required for IL-21-induced ERK1/2 activation. -- Abstract: 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.

• OSTI ID: 22207807
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 420, Issue 3; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CELL DIFFERENTIATION
CELL PROLIFERATION
DENDRITES
MESSENGER-RNA
MUTANTS
NATURAL KILLER CELLS
OXYGEN
PROTEINS