title: Control of Oxidative Stress and Generation of Induced Pluripotent Stem Cell-like Cells by Jun Dimerization Protein 2.
abstract: We report here that the Jun dimerization protein 2 (JDP2) plays a critical role as a cofactor for the transcription factors nuclear factor-erythroid 2-related factor 2 (Nrf2) and MafK in the regulation of the antioxidants and production of reactive oxygen species (ROS). JDP2 associates with Nrf2 and MafK (Nrf2-MafK) to increase the transcription of antioxidant response element-dependent genes. Oxidative-stress-inducing reagent led to an increase in the intracellular accumulation of ROS and cell proliferation in Jdp2 knock-out mouse embryonic fibroblasts. In Jdp2-Cre mice mated with reporter mice, the expression of JDP2 was restricted to granule cells in the brain cerebellum. The induced pluripotent stem cells (iPSC)-like cells were generated from DAOY medulloblastoma cell by introduction of JDP2, and the defined factor OCT4. iPSC-like cells expressed stem cell-like characteristics including alkaline phosphatase activity and some stem cell markers. However, such iPSC-like cells also proliferated rapidly, became neoplastic, and potentiated cell malignancy at a later stage in SCID mice. This study suggests that medulloblastoma cells can be reprogrammed successfully by JDP2 and OCT4 to become iPSC-like cells. These cells will be helpful for studying the generation of cancer stem cells and ROS homeostasis.
authors.affiliation: Division of Hematology-Oncology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan. chiouss@kmu.edu.tw.
authors.forename: Shyh-Shin
authors.initials: SS
authors.lastname: Chiou
authors.forename: Sophie Sheng-Wen
authors.initials: SS
authors.lastname: Wang
authors.forename: Deng-Chyang
authors.initials: DC
authors.lastname: Wu
authors.forename: Ying-Chu
authors.initials: YC
authors.lastname: Lin
authors.forename: Li-Pin
authors.initials: LP
authors.lastname: Kao
authors.forename: Kung-Kai
authors.initials: KK
authors.lastname: Kuo
authors.forename: Chun-Chieh
authors.initials: CC
authors.lastname: Wu
authors.forename: Chee-Yin
authors.initials: CY
authors.lastname: Chai
authors.forename: Cheng-Lung Steve
authors.initials: CL
authors.lastname: Lin
authors.forename: Cheng-Yi
authors.initials: CY
authors.lastname: Lee
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Liao
authors.forename: Kenly
authors.initials: K
authors.lastname: Wuputra
authors.forename: Ya-Han
authors.initials: YH
authors.lastname: Yang
authors.forename: Shin-Wei
authors.initials: SW
authors.lastname: Wang
authors.forename: Chia-Chen
authors.initials: CC
authors.lastname: Ku
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Shigeo
authors.initials: S
authors.lastname: Saito
authors.forename: Hitomi
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Naoto
authors.initials: N
authors.lastname: Yamaguchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Miyoshi
authors.forename: Chang-Sheng
authors.initials: CS
authors.lastname: Lin
authors.forename: Richard
authors.initials: R
authors.lastname: Eckner
authors.forename: Kazunari K
authors.initials: KK
authors.lastname: Yokoyama