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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
51
pubmed:dateCreated
2006-12-18
pubmed:abstractText
The N-myc downstream-regulated gene 1 (ndrg1) is highly expressed in N-myc knock-out mice through an unknown regulatory mechanism. As one member of the human NDRG gene family, NDRG2 encodes a protein highly homologous to Ndrg1. However, it is uncertain whether the expression of human NDRG2 is regulated by Myc because mouse ndrg2 and -3 are not affected by Myc. In this study, we provide the novel evidence that the expression of human NDRG2 is down-regulated by Myc via transcriptional repression. A high level of NDRG2 was observed as Myc expression was reduced in differentiated cells, whereas a low level of NDRG2 was shown following increased Myc expression upon serum stimulation. The ectopic expression of c-Myc dramatically reduces the cellular Ndrg2 protein and mRNA level. We further identified the core promoter region of NDRG2 that is required for Myc repression on NDRG2 transcription, and we verified the interaction of Myc with the core promoter region both in vitro and in vivo. Moreover, the c-Myc-mediated repression of NDRG2 requires association with Miz-1, and possibly the recruitment of other epigenetic factors, such as histone deacetylases, to the promoter. The regulatory function of Myc on NDRG2 gene expression implicated the role of the Ndrg2 in regulating cell differentiation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
281
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
39159-68
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:17050536-Animals, pubmed-meshheading:17050536-Caco-2 Cells, pubmed-meshheading:17050536-Cell Differentiation, pubmed-meshheading:17050536-DNA-Binding Proteins, pubmed-meshheading:17050536-Down-Regulation, pubmed-meshheading:17050536-Epigenesis, Genetic, pubmed-meshheading:17050536-Gene Expression Regulation, pubmed-meshheading:17050536-HL-60 Cells, pubmed-meshheading:17050536-HeLa Cells, pubmed-meshheading:17050536-Humans, pubmed-meshheading:17050536-Kruppel-Like Transcription Factors, pubmed-meshheading:17050536-Mice, pubmed-meshheading:17050536-NIH 3T3 Cells, pubmed-meshheading:17050536-Promoter Regions, Genetic, pubmed-meshheading:17050536-Proteins, pubmed-meshheading:17050536-Proto-Oncogene Proteins c-myc, pubmed-meshheading:17050536-Transcription Factors, pubmed-meshheading:17050536-Tumor Suppressor Proteins, pubmed-meshheading:17050536-U937 Cells
pubmed:year
2006
pubmed:articleTitle
The repression of human differentiation-related gene NDRG2 expression by Myc via Miz-1-dependent interaction with the NDRG2 core promoter.
pubmed:affiliation
Institute of Molecular Biology and the State Key Laboratory of Cancer Biology, Fourth Military Medical University, 710032 Xi'an, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't