Involvement of PLAGL2 in activation of iron deficient- and hypoxia-induced gene expression in mouse cell lines

Furukawa, Takako; Adachi, Yasushi; Fujisawa, Jun–ichi; Kambe, Taiho; Yamaguchi-Iwai, Yuko; Sasaki, Ryuzo; Kuwahara, Jun; Ikehara, Susumu; Tokunaga, Rikio; Taketani, Shigeru

doi:10.1038/sj.onc.1204647

Cited by 55 publications

(74 citation statements)

References 32 publications

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“…However, it was reported that PLAGL2, possibly by association with HIF-1, may also have apoptotic role since it caused induction of Nip3 by promoter activation, leading to apoptosis of Balb/c3T3 fibroblasts and Neuro2a neuroblastoma cells (Mizutani et al, 2002). In a related experiment, PLAGL2 mRNA was found to be induced upon iron deficiency or hypoxia in mouse macrophage cell line RAW264.7, mouse erythroleukemia (MEL) cells, and Balb/c3T3 cells (Furukawa et al, 2001). Therefore, the report proposed that PLAGL2 is involved in the cell-cycle arrest and apoptosis of tumor cells by regulating iron depletion-or hypoxia-inducible gene expression (Furukawa et al, 2001).…”

Section: Role Of the Plag Family Members As Nuclear Transcription Factormentioning

confidence: 96%

“…In a related experiment, PLAGL2 mRNA was found to be induced upon iron deficiency or hypoxia in mouse macrophage cell line RAW264.7, mouse erythroleukemia (MEL) cells, and Balb/c3T3 cells (Furukawa et al, 2001). Therefore, the report proposed that PLAGL2 is involved in the cell-cycle arrest and apoptosis of tumor cells by regulating iron depletion-or hypoxia-inducible gene expression (Furukawa et al, 2001). In addition, PLAGL2 was also able to transactivate the surfactant protein-C (SP-C), a protein whose expression occurs principally in type II pneumocytes located in the distal lung alveolae .…”

Section: Role Of the Plag Family Members As Nuclear Transcription Factormentioning

confidence: 99%

“…PLAG1, however, shows a single band of about 7.5 kb in fetal tissue but is not detectable by Northern blot in fetal brain (Kas et al, 1997. PLAGL2 was shown in another study to be ubiquitously expressed in various tissues, with a relatively high expression in lung, spleen, and testis (Furukawa et al, 2001). …”

Section: Potential Role In Tumorigenicitymentioning

confidence: 99%

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LOT1 (ZAC1/PLAGL1) and its family members: Mechanisms and functions

Abdollahi

2006

Journal Cellular Physiology

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Lost-on-transformation 1 (LOT1) (PLAGL1/ZAC1) is a member of the novel subfamily of zinc-finger transcription factors, designated as PLAG family. The other members in this group include PLAG1 and PLAGL2, which share high homology with each other and with LOT1, particularly in their zinc-finger amino-terminal region. They are structurally similar but functionally different. For example, the LOT1 gene encodes a growth suppressor protein and is localized on human chromosome 6q24-25, a chromosomal region that is frequently deleted in many types of human cancers. The gene is maternally imprinted and is linked to developmental disorders such as growth retardation and transient neonatal diabetes mellitus (TNDM). LOT1 is a target of growth factor signaling pathway(s) and silenced by epigenetic mechanisms, as well as by the loss of heterozygosity in different tumor tissues. PLAG1 is a protooncogene that is localized on chromosome 8q12 and was found to be a target of several types of chromosomal rearrangement including the one identified in pleomorphic adenomas of the salivary gland. Since the discovery of the PLAG family members in 1997, much has been learned about their structure and function, as are summarized in this review. While the available data suggest that these proteins may play important roles in regulating normal physiological functions in the mammals, a great deal more about their signaling pathway(s), potential role in the complex pathologies such as cancer and developmental disorders, and functional relationship between different family members and splice variants still remains to be uncovered.

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Section: Role Of the Plag Family Members As Nuclear Transcription Factormentioning

confidence: 96%

Section: Role Of the Plag Family Members As Nuclear Transcription Factormentioning

confidence: 99%

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LOT1 (ZAC1/PLAGL1) and its family members: Mechanisms and functions

Abdollahi

2006

Journal Cellular Physiology

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“…5,6 Furthermore, it is known that the upregulation of HIF-1␣ by potent Fe chelators diverges from the angiogenic pathway to induce apoptosis. 9,10 In fact, a study by Furukawa et al 12 using DFO showed HIF-1␣-dependent upregulation of the PLAGL2 transcription factor that transactivates Nip3 to cause cell death. 12,13 This principle has been demonstrated recently using the potent mycobacterial Fe chelator, desferri-exochelin.…”

Section: Dear Sirmentioning

confidence: 99%

Competing pathways of iron chelation: Angiogenesis or anti‐tumor activity: Targeting different molecules to induce specific effects

Richardson

2004

Intl Journal of Cancer

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“…Early studies showed that EPO production is markedly up-regulated by transition metals including cobalt, manganese and nickel, which can be incorporated into protoporphyrin IX, and have suggested that the oxygen sensor involved in the synthesis of EPO is a hemeprotein which binds oxygen (Goldberg et al 1988(Goldberg et al , 1990). Furthermore, iron should play an important role in the oxygen sensing system since the increased expression of HIF-1, followed by the induction of EPO synthesis, was observed under iron-depleted as well as hypoxic conditions (Furukawa et al 2001;Mizutani et al 2002). Iron can alter levels of chemical messengers in the oxygen-sensing pathway since iron catalyzes the production of ROS by the Fenton reaction.…”

Section: Contribution Of Iron and Heme To Oxygen-sensing Systemmentioning

confidence: 99%

Aquisition, Mobilization and Utilization of Cellular Iron and Heme: Endless Findings and Growing Evidence of Tight Regulation

Taketani

2005

Tohoku J. Exp. Med.

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100

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Iron is fastidiously utilized by living cells, since it is an essential element, but is toxic in excess. Cells take up iron via a transferrin-transferrin receptor-dependent endocytotic process. The iron thus taken up is used for essential biological functions including oxygen transport, electron transfer, and DNA synthesis. The intracellular level of iron is tightly controlled, through regulation of the cellular uptake of iron and the sequestering of low molecular labile iron into the storage protein ferritin. The known proteins of iron transport and storage, transferrin, transferrin receptor and ferritin, have been recently linked with a number of newly identified proteins that are responsible for inherited diseases of iron metabolisms and play critical roles in the maintenance of iron homeostasis. These proteins are involved in regulation of intracellular levels of iron, iron transport, and heme transport and the oxygen-dependent regulation of gene expression. On the other hand, most iron is transported into mitochondria and immediately used for the biosynthesis of heme in erythroid cells. The heme biosynthesis in mitochondria is coupled with the supply of iron, and the heme, exported from mitochondria, is utilized as prosthetic groups of hemeproteins. Furthermore, non-erythroid and erythroid cells possess the different regulatory systems for the biosynthesis of heme; iron positively regulates the biosynthesis in erythroid cells while heme negatively regulates it in non-erythroid cells. Because of the toxicity and insolubility of heme, the intracellular level of uncommitted heme is maintained at a low concentration (< 10 -9 M). The influx and efflux of heme also help to prevent cytotoxicity. Finally, heme-binding transcriptional factors such as Bach1 and NPAS2 regulate the transcription of several genes involved in the synthesis and degradation of heme-hemeproteins. The discovery of new molecules related to disorders of iron and heme metabolism is ascribable to a complete mechanistic understanding of the cellular network of iron homeostasis. The network of interactions that link iron and heme metabolisms with functions of cellular regulation involving oxidative stress and inflammations contributes to new insights into clinical aspects of disorders.

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Involvement of PLAGL2 in activation of iron deficient- and hypoxia-induced gene expression in mouse cell lines

Cited by 55 publications

References 32 publications

LOT1 (ZAC1/PLAGL1) and its family members: Mechanisms and functions

LOT1 (ZAC1/PLAGL1) and its family members: Mechanisms and functions

Competing pathways of iron chelation: Angiogenesis or anti‐tumor activity: Targeting different molecules to induce specific effects

Aquisition, Mobilization and Utilization of Cellular Iron and Heme: Endless Findings and Growing Evidence of Tight Regulation

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