Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0008569
Title: Interferon-inducible IFI16, a negative regulator of cell growth, down-regulates expression of human telomerase reverse transcriptase (hTERT) gene
Authors: Song L.L.
Ponomareva L.
Shen H. 
Duan X.
Alimirah F.
Choubey D.
Keywords: antimitotic agent
aphidicolin
cgk 1026
interferon
interferon inducible IFI16 protein
luciferase
messenger RNA
Myc protein
protein
telomerase
telomerase reverse transcriptase
unclassified drug
IFI16 protein, human
messenger RNA
nuclear protein
phosphoprotein
telomerase
TERT protein, human
article
cell cycle progression
cell growth
cell interaction
cell stimulation
controlled study
diploidy
enzyme activity
fibroblast
gene expression regulation
gene overexpression
growth inhibition
HeLa cell
human
human cell
immunoblotting
real time polymerase chain reaction
receptor down regulation
reporter gene
signal transduction
steady state
telomeric repeat amplification protocol
transcription regulation
cell division
cell line
down regulation
gene silencing
genetic transcription
genetics
metabolism
oncogene myc
physiology
Cell Division
Cell Line
Down-Regulation
Gene Expression Regulation, Enzymologic
Gene Knockdown Techniques
Genes, myc
Hela Cells
Humans
Nuclear Proteins
Phosphoproteins
RNA, Messenger
Telomerase
Transcription, Genetic
Issue Date: 2010
Citation: Song L.L., Ponomareva L., Shen H., Duan X., Alimirah F., Choubey D. (2010). Interferon-inducible IFI16, a negative regulator of cell growth, down-regulates expression of human telomerase reverse transcriptase (hTERT) gene. PLoS ONE 5 (1) : e8569. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0008569
Abstract: Background: Increased levels of interferon (IFN)-inducible IFI16 protein (encoded by the IFI16 gene located at 1q22) in human normal prostate epithelial cells and diploid fibroblasts (HDFs) are associated with the onset of cellular senescence. However, the molecular mechanisms by which the IFI16 protein contributes to cellular senescence-associated cell growth arrest remain to be elucidated. Here, we report that increased levels of IFI16 protein in normal HDFs and in HeLa cells negatively regulate the expression of human telomerase reverse transcriptase (hTERT) gene. Methodology/Principal Findings: We optimized conditions for real-time PCR, immunoblotting, and telomere repeat amplification protocol (TRAP) assays to detect relatively low levels of hTERT mRNA, protein, and telomerase activity that are found in HDFs. Using the optimized conditions, we report that treatment of HDFs with inhibitors of cell cycle progression, such as aphidicolin or CGK1026, which resulted in reduced steady-state levels of IFI16 mRNA and protein, was associated with increases in hTERT mRNA and protein levels and telomerase activity. In contrast, knockdown of IFI16 expression in cells increased the expression of c-Myc, a positive regulator of hTERT expression. Additionally, over-expression of IFI16 protein in cells inhibited the c-Myc-mediated stimulation of the activity of hTERT-luc-reporter and reduced the steady-state levels of c-Myc and hTERT. Conclusions/Significance: These data demonstrated that increased levels of IFI16 protein in HDFs down-regulate the expression of hTERT gene. Our observations will serve basis to understand how increased cellular levels of the IFI16 protein may contribute to certain aging-dependent diseases.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/161822
ISSN: 19326203
DOI: 10.1371/journal.pone.0008569
Appears in Collections:Elements
Staff Publications

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1371_journal_pone_0008569.pdf375.71 kBAdobe PDF

OPEN

NoneView/Download

SCOPUSTM   
Citations

28
checked on Aug 5, 2020

Page view(s)

77
checked on Aug 6, 2020

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.