Document Detail


Evidence of extra-telomeric effects of hTERT and its regulation involving a feedback loop.
MedLine Citation:
PMID:  17134697     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The human telomerase reverse transcriptase (hTERT) is the catalytic subunit of the enzyme telomerase which is responsible for telomeric maintenance and extension. Using RNA interference to knock down hTERT mRNA expression, we provide evidence that hTERT exerts extra-telomeric effects on the cell cycle and on its own regulatory proteins, specifically: p53 and p21. We tested our hypothesis that hTERT regulates its own expression through effects on upstream regulatory genes using transformed human embryonic kidney (HEK 293) cells, p53 and p16(INK4a) null human ovarian cancer SKOV-3 cells, and p53-null MDA-MB-157 human mammary cancer cells. In HEK 293 cells, hTERT knockdown resulted in elevated p53 and p21 transcription and a decrease in cellular proliferation. Similar results were observed in the MDA-MB-157 cell line where p21 was upregulated, correlating with cell growth inhibition. In contrast, we observed a decrease in expression of p21 in SKOV-3 cells with hTERT knockdown and cell growth appeared to be unaffected. These findings suggest that hTERT may be involved in a feedback loop system, thereby playing a role in its own regulation.
Authors:
Serene R Lai; Amanda P Cunningham; Vu Q Huynh; Lucy G Andrews; Trygve O Tollefsbol
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-10-25
Journal Detail:
Title:  Experimental cell research     Volume:  313     ISSN:  0014-4827     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2007-01-12     Completed Date:  2007-03-09     Revised Date:  2014-09-24    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  322-30     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Cells, Cultured
Cyclin-Dependent Kinase Inhibitor p21 / genetics*
Feedback, Physiological / genetics*
Gene Expression Regulation*
Humans
RNA Interference
RNA, Messenger / metabolism
Telomerase / antagonists & inhibitors,  genetics*,  physiology*
Telomere / enzymology
Tumor Suppressor Protein p53 / genetics*
Grant Support
ID/Acronym/Agency:
R21 CA114019/CA/NCI NIH HHS; U54 CA100949/CA/NCI NIH HHS; U54 CA100949-010007/CA/NCI NIH HHS; U54 CA118948/CA/NCI NIH HHS; U54 CA118948-010001/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/RNA, Messenger; 0/Tumor Suppressor Protein p53; EC 2.7.7.49/TERT protein, human; 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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