1. Control of Oxidative Stress and Generation of Induced Pluripotent Stem Cell-like Cells by Jun Dimerization Protein 2
- Author
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Ying-Chu Lin, Shyh-Shin Chiou, Chee-Yin Chai, Shin-Wei Wang, Kazunari K. Yokoyama, Cheng-Lung Steve Lin, Yu-Mei Liao, Cheng-Yi Lee, Kenly Wuputra, Kung-Kai Kuo, Shigeo Saito, Chia-Chen Ku, Deng-Chyang Wu, Hiroyuki Miyoshi, Naoto Yamaguchi, Ya-Han Yang, Chang-Sheng Lin, Chun-Chieh Wu, Sophie Wang, Hitomi Hasegawa, Li-Pin Kao, Yukio Nakamura, and Richard Eckner
- Subjects
Cancer Research ,Induced stem cells ,biology ,Cellular differentiation ,anti oxidation ,ROS ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Stem cell marker ,medulloblastoma ,lcsh:RC254-282 ,Embryonic stem cell ,Article ,Cell biology ,Endothelial stem cell ,Oncology ,Jun dimerization protein 2 ,Immunology ,Jun dimerization protein ,biology.protein ,oxidative stress ,iPSC-like cells ,Induced pluripotent stem cell ,Adult stem cell - 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.
- Published
- 2013