Document Detail


Activation of telomerase rna gene promoter activity by NF-Y, Sp1, and the retinoblastoma protein and repression by Sp3.
MedLine Citation:
PMID:  11228546     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Expression of the human telomerase RNA component gene, hTERC is essential for telomerase activity. The hTERC gene is expressed during embryogenesis and then downregulated during normal development, leaving most adult somatic cells devoid of hTERC expression. During oncogenesis, however, hTERC is re-expressed consequently contributing to the unrestricted proliferative capacity of many human cancers. Thus the identification of the molecular basis for the regulation of the telomerase RNA component gene in normal cells and its deregulation in cancer cells is of immediate interest. We have previously cloned the hTERC promoter and in this study have identified several transcription factors that modulate the expression of hTERC. We demonstrate that NF-Y binding to the CCAAT region of the hTERC promoter is essential for promoter activity. Sp1 and the retinoblastoma protein (pRb) are activators of the hTERC promoter and Sp3 is a potent repressor. These factors appear to act in a species-specific manner. Whereas Sp1 and Sp3 act on the human, bovine, and mouse TERC promoters, pRb activates only the human and bovine promoter, and NF-Y is only essential for the human TERC gene.
Authors:
J Q Zhao; R M Glasspool; S F Hoare; A Bilsland; I Szatmari; W N Keith
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neoplasia (New York, N.Y.)     Volume:  2     ISSN:  1522-8002     ISO Abbreviation:  Neoplasia     Publication Date:    2000 Nov-Dec
Date Detail:
Created Date:  2001-03-06     Completed Date:  2002-04-01     Revised Date:  2013-06-11    
Medline Journal Info:
Nlm Unique ID:  100886622     Medline TA:  Neoplasia     Country:  United States    
Other Details:
Languages:  eng     Pagination:  531-9     Citation Subset:  IM    
Affiliation:
CRC Department of Medical Oncology, University of Glasgow, CRC Beatson Laboratories, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
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MeSH Terms
Descriptor/Qualifier:
Animals
Base Sequence
Binding Sites
CCAAT-Binding Factor / metabolism*
Cattle
DNA Primers / chemistry
DNA-Binding Proteins / pharmacology*
Electrophoretic Mobility Shift Assay
Gene Expression Regulation, Enzymologic / drug effects*
HeLa Cells / drug effects,  enzymology
Humans
Mice
Molecular Sequence Data
Mutagenesis, Site-Directed
Polymerase Chain Reaction
RNA / genetics*,  metabolism
RNA, Messenger / metabolism
Retinoblastoma Protein / pharmacology*
Sequence Deletion
Sp1 Transcription Factor / pharmacology*
Sp3 Transcription Factor
Telomerase / genetics*,  metabolism
Transcription Factors / pharmacology*
Transcription, Genetic
Transfection
Chemical
Reg. No./Substance:
0/CCAAT-Binding Factor; 0/DNA Primers; 0/DNA-Binding Proteins; 0/RNA, Messenger; 0/Retinoblastoma Protein; 0/SP3 protein, human; 0/Sp1 Transcription Factor; 0/Sp3 protein, mouse; 0/Transcription Factors; 0/telomerase RNA; 148710-94-5/Sp3 Transcription Factor; 63231-63-0/RNA; EC 2.7.7.49/Telomerase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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