title: Apurinic/apyrimidinic endonuclease1/redox factor-1 (Ape1/Ref-1) is essential for IL-21-induced signal transduction through ERK1/2 pathway.
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.
authors.affiliation: Department of Immunology, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors.forename: Farha M
authors.initials: FM
authors.lastname: Juliana
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Nara
authors.forename: Tadashi
authors.initials: T
authors.lastname: Onoda
authors.forename: Mizanur
authors.initials: M
authors.lastname: Rahman
authors.forename: Akemi
authors.initials: A
authors.lastname: Araki
authors.forename: Lianjin
authors.initials: L
authors.lastname: Jin
authors.forename: Hodaka
authors.initials: H
authors.lastname: Fujii
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Tanaka
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Hoshino
authors.forename: Hironobu
authors.initials: H
authors.lastname: Asao
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000235:genetics*; D051379:Mice; D015398:Signal Transduction / Q000235:genetics; D000098546:Interleukin-21
chemical_list: D007378:Interleukins; C486216:Apex1 protein, mouse; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D000098546:Interleukin-21