Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2000-3-31
pubmed:abstractText
Activation of telomerase, which has been frequently associated with cellular immortality, may constitute a key step in the development of human cancer. De-repression in the expression of its catalytic subunit hTERT gene has been proposed to directly link to the telomerase activation in tumor cells. Little is known about the mechanism how the hTERT gene is repressed in telomerase-negative mortal cells. This study was conducted, using an expression cloning approach, with the aim of identifying the gene(s) responsible for repressing the hTERT gene expression. Using this genetic screen, we isolated the transcription factor Mad as a repressor. Mutation of its DNA binding sites caused significant de-repression of hTERT promoter activity in mortal cells. This Mad-mediated repression of the hTERT promoter in mortal cells was counteracted by ectopic expression of Myc. The antagonism between Mad and Myc was also observed with an endogenous hTERT promoter. Their potential roles in differential hTERT promoter activities were further supported by the relative amounts of Mad and Myc proteins detected in immortal and mortal cells. Thus, Mad may be a direct negative regulator of hTERT in mortal cells and this repression mechanism can be inhibited by induction of Myc in immortal cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
9
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1485-90
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Identification of Mad as a repressor of the human telomerase (hTERT) gene.
pubmed:affiliation
National Creative Research Initiative Center for Genetic Reprogramming, Institute for Molecular Biology and Genetics, Seoul National University, Seoul 151-742, Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't