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Egr-1 mediates hypoxia-inducible transcription of the NDRG1 gene through an overlapping Egr-1/Sp1 binding site in the promoter

, : Egr-1 mediates hypoxia-inducible transcription of the NDRG1 gene through an overlapping Egr-1/Sp1 binding site in the promoter. Cancer Research 67(19): 9125-9133

N-myc down-regulated gene 1 (NDRG1/Cap43) is inducible by a variety of environmental stressors, including hypoxia. The present study identified a cis-acting element mediating the transactivation of the NDRG1 gene in murine RAW264.7 macrophage cells treated with hypoxia or deferoxamine, an iron chelator mimicking hypoxia. Through a series of deletions of the promoter of NDRG1 luciferase constructs, a minimal cis-acting element conferring inducibility by hypoxia and deferoxamine was localized to an early growth response I (Egr-1) and Sp1 overlapping binding site. Electrophoretic mobility shift assay, antibody supershift assay, and mutations of the Egr-1 binding site confirmed the specific binding of Egr-1 protein to this Egr-1/Sp1 motif. In addition, hypoxia increased the level of Egr-1 protein that correlated with induction of NDRG1 expression at both RNA and protein levels. Transient transfection of the Egr-1 gene into HeLa cells also resulted in up-regulation of the NDRG1 mRNA. The role of Egr-1 was further verified by mutations in the Egr-1 binding site, which reduced promoter inducibility by hypoxia and deferoxamine. Furthermore, the induction of NDRG1 expression by hypoxia and deferoxamine was diminished by RNA interference knockdown of Egr-1 gene expression and in Egr-1(-/-) mouse embryonic fibroblasts (MEF) compared with Egr-1(-/-) METs. These results showed for the first time that Egr-1 regulates NDRG1 transcription through an overlapping Egr-1/Sp1 binding site that acts as a major site of positive regulation of the NDRG1 promoter by hypoxia signaling.

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Accession: 015682123

PMID: 17909017

DOI: 10.1158/0008-5472.CAN-07-1525

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Sarkar, A.; Fujita, H., 1994: Better technique for nutritive evaluation of mulberry leaves for silkworm, Bombyx mori. The nutritive values of several varieties of mulberry were evaluated based on the production efficiency of cocoon shells (PECS) by Bombyx mori. The highest PECS value occurred on the mulberry variety Hachinose. B. mori reared on the leaves of this...

Drazenovic, Vladimir; Ilic, Ankica; Sim, Renata; Bozikov, Jadranka; Mlinaric Galinovic, Gordana, 2003: Immune response to influenza vaccine -like, A/Moscow/10/99 -like, and B/Beijing/184/93+ B/Yamanashi/166/98-like in the elderly. Background and Purpose: The purpose of this paper was to ascertain immunologic response to the vaccine administered to the elderly. Hemagglutination-inhibition (HI) antibodies are protective antibodies. Immune response to the administered vaccine...

Horisaki, A.; Tanaka, N.; Niikura, S., 2003: The effectiveness of insect-pollination test to evaluate the level of self-incompatibility and their genetic analysis in radish (Raphanus sativus L.). We have tried an insect-pollination self-incompatibility (SI) test to strictly evaluate the level of SI as a model for the actual F< sub>1</ sub> seed production field using radish as experimental material. Twelve inbred lines, homozyg...

Stiller, M., 1986: A new genus, Proekoides (Homoptera: Cicadellidae) described from fynbos in South Africa. A new genus, Proekoides, is proposed and four new species are described viz. P. hawekwae, P. cedarbergensis, P. piketensis and P. koebergis.

Litvinova, N. M., 1984: A remarkable new species of the genus Ophiopyrgus Echinodermata, Ophiuroidea with comments on this genus. Zoologicheskii Zhurnal 63.10: 1585-1588

K. J. Rankine; N. Sivakugan; R. Cowling, 2006: Emplaced geotechnical characteristics of hydraulic fills in a number of Australian mines. Hydraulic fills used in Australian mines have similar grain size distributions whilst having quite different specific gravity values, typically in the range of 2.7–4.4. When produced and distributed in slurry at 65–75% by solid content, they s...

ChoiYangHun; KweonJiHyang; JeongYoungMi; KwonSoonbuhm; KimHyungSoo, 2010: Effects of magnetic ion-exchange resin addition during coagulation on floc properties and membrane filtration. The application of magnetic ion-exchange resin (MIEX) during chemical coagulation was investigated for the removal of organic matters responsible for fouling in membrane processes. Two different coagulants were used - polyaluminium chloride (PACl)...

Sapegin D. D.; Karpov N. M.; Nikitin A. A., 1990: Geomechanical modelling of joints in rock foundations of structures. Pages 713-717 1990

Chen L.F.; Palmer R.G., 1985: Cytological studies of triploids and their progeny from male sterile ms 1 soybean glycine max. Triploids (2n = 3X = 60) were obtained from genetic male-sterile (ms1 ms1) soybean [Glycine max (L.) Merr.] plants. Meiosis, pollen fertility, and chromosome number of their progeny were studied. Studies of meiosis in fertile and sterile triploids...

Cavallo, D. F.; Sanchez, C. E., 1986: Tourism, external debt and the integration of Latin America. The challenge of growth through exports and reducing debt, which faces Latin American countries today, leads to the search for imaginative and dynamic solutions. Tourism can offer a solution if it is given priority in government policy. The type o...