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.

Reprogramming Antagonizes the Oncogenicity of HOXA13-Long Noncoding RNA HOTTIP Axis in Gastric Cancer Cells

“…We used transcription factors, JDP2 and OCT4, to induce reprogramming and generate iPSCs as described previously , because it was not feasible to use the standard four Yamanaka factors to generate stem cell‐like colonies (data not shown) in the normal human gastric mucosa cell line CSN and its derived CS12 cancer cells . Three weeks after electroporation of JDP2 and OCT4, small, packed, domed iPSC‐like colonies were detected (Fig.…”

“…We have shown that the Jun dimerization protein 2 (JDP2) is a modulator of wingless‐related integration site signaling pathway and works together with octamer‐binding protein 4 (OCT4) for the reprogramming of medulloblastoma to generate induced pluripotent stem cell (iPSC)‐like cells (iPSLCs) . Liu et al also reported that JDP2 reprograms the somatic cells into the iPSCs through the five non‐Yamanaka factors (Id1, Jhdm1b, Lrh1, Sall4, and Glis1).…”

Effects of mutant TDP-43 on the Nrf2/ARE pathway and protein expression of MafK and JDP2 in NSC-34 cells

“…Hence, JDP2 plays important roles in a variety of physiological and pathological processes in cells (Aronheim et al, 1997;Katz et al, 2001;Jin et al, 2002Jin et al, , 2006Rasmussen et al, 2009). Studies have shown that JDP2 acts as a cofactor in gene transcription and plays an important role in the Nrf2/ARE/MafKmediated anti-oxidative stress transcriptional pathway (Chiou et al, 2013;Tanigawa et al, 2013). JDP2 directly binds to the core sequence of ARE and Nrf2-MafK through the basic leucine zipper region to promote Nrf2-MafK complex initiation of DNA activity.…”

“…JDP2 directly binds to the core sequence of ARE and Nrf2-MafK through the basic leucine zipper region to promote Nrf2-MafK complex initiation of DNA activity. Also, JDP2 binds to ARE to promote expression of ARE-associated genes (Chiou et al, 2013;Tanigawa et al, 2013). Therefore, JDP2 plays an important role in protecting cells against oxidative stress.…”

Application of Cancer Cell Reprogramming Technology to Human Cancer Research

“…Summary of studies of reprogramming of human cancer cells to induce pluripotent stem cells (iPSC). Recent reports also demonstrated the success in reducing the tumorigenicity of cancer cells (51,(80)(81)(82), or not changing the plasticity of cancer cells (80,81,(83)(84)(85), even exhibiting strong cancerous features such as cancer stem cells (81), even these heterogeneous outputs are due to the status of p53 (86). Modified from the PDAC, Pancreatic ductal adenocarcinoma; MDS, myelodysplastic syndromes; LFS, Li-Fraumeni syndrome; GBM, glioblastoma multiforme; CML, chronic myeloid leukemia; C-MET, Tyrosine-protein kinase MET; DOX, doxycycline; ESCs, embryonic stem cells; GM-CSF, granulocyte macrophage colony-stimulating factor; HIF1a, hypoxia-inducible factor 1-alpha; HIF 2a, hypoxia-inducible factor 2-alpha; K, KLF4; M, c-MYC; MAPK, mitogen-activated protein kinases; N, NANOG; O, Octamer-binding protein 4 (OCT4); S, SRY(sex determining region Y)-box 2 (SOX2); shp53, short hairpin p53.…”