| Inducible activation of IFI 16 results in suppression of telomerase activity, growth suppression and induction of cellular senescence. | |
| | |
MedLine Citation:
|
PMID: 19885868 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Expression of the human HIN-200 family member IFI 16 has been reported to suppress cell growth and contribute to the onset of cellular senescence. However the molecular events involved in this process have not been fully characterised. We fused IFI 16 to the estrogen receptor ligand-binding domain to establish an inducible model for studying the molecular events that cause these phenomena. In cells induced to express the ER-IFI 16 within the nucleus there was a decrease in cellular proliferation and concomitant growth arrest in the G1 phase of the cell cycle. Unlike previous reports, this did not appear to involve the p53-p21(WAF1/CIP1)-cdk2-pRb pathway. Following nuclear expression of ER-IFI 16 we noted senescence-like morphological changes and expression of senescence-associated beta-galactosidase in growth arrested cells. Importantly, we also found a marked reduction in telomerase activity in arrested cells compared to controls. Moreover, IFI 16 and hTERT co-localised within the nucleus and these two proteins physically interacted in vivo and in vitro. Together, these data suggest that IFI 16 may act as an endogenous regulator of telomerase activity and, through its interaction with hTERT, contributes to the inhibition of proliferation and induces a senescence-like state. |
| | |
Authors:
|
Christopher J P Clarke; Linda L Hii; Jessica E Bolden; Ricky W Johnstone |
Related Documents
:
|
15604268 - Immortalization of human bronchial epithelial cells in the absence of viral oncoproteins. 10411308 - Loss of several cell functions including okadaic acid-induced apoptosis after multiple ... 10784448 - Extension of cell life-span and telomere length in animals cloned from senescent somati... 3144638 - Cell surface oligosaccharide modulation during differentiation: iv. normal and transfor... 15859948 - Volume regulation in cortical collecting duct cells: role of aqp2. 20035008 - Induction of salmonella pathogenicity island 1 under different growth conditions can af... |
Publication Detail:
|
Type: Journal Article |
Journal Detail:
|
Title: Journal of cellular biochemistry Volume: 109 ISSN: 1097-4644 ISO Abbreviation: J. Cell. Biochem. Publication Date: 2010 Jan |
Date Detail:
|
Created Date: 2009-12-28 Completed Date: 2010-03-02 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8205768 Medline TA: J Cell Biochem Country: United States |
Other Details:
|
Languages: eng Pagination: 103-12 Citation Subset: IM |
Affiliation:
|
Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Blotting, Western Cell Aging / physiology* Cell Cycle Proteins / metabolism Cell Line, Tumor Cell Proliferation* Fluorescent Antibody Technique Humans Immunoprecipitation Nuclear Proteins / metabolism* Phosphoproteins / metabolism* Telomerase / metabolism* |
| Chemical | |
Reg. No./Substance:
|
0/Cell Cycle Proteins; 0/Nuclear Proteins; 0/Phosphoproteins; 148998-64-5/IFI16 protein, human; EC 2.7.7.49/Telomerase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: The nucleosome binding protein HMGN3 is expressed in pancreatic alpha-cells and affects plasma gluca...
Next Document: Restricted dead-end elimination: Protein redesign with a bounded number of residue mutations.