Journal article
Interferon regulatory factor 3 activates p53-dependent cell growth inhibition
Cancer letters, Vol.242(2), pp.215-221
10/28/2006
DOI: 10.1016/j.canlet.2005.11.003
PMID: 16513254
Abstract
Interferon regulatory factor 3 (IRF3) is a transcriptional factor that plays a crucial role in activation of innate immunity and inflammation in response to viral infection. We investigated the biological function of IRF3 overexpressed in somatic cells such as fibroblasts and astrocytes. Similar to overexpression of oncogenic H-ras in the normal human fibroblast, overexpression of IRF3 in human fibroblast BJ cells was shown to decrease cell growth and increase senescence-associated β-galactosidase activity by activating a p53 tumor suppressor. BCNU, a DNA damage agent, further accelerated p53 function and cell death in the IRF3-overexpressed BJ cells compared to control BJ cells, without increased expression of IRF3 target genes. IRF3 failed to activate p53 function and cell growth inhibition in BJ cells downregulating p53 by RNAi-mediated p53 knockdown. Furthermore, enforced expression of IRF3 did not show any effect of cell growth inhibition in astrocytes or embryonic fibroblasts derived from the p53−/− mouse. When compared to control BJ cells, BJ cells which downregulated IRF3 by RNAi-mediated IRF3 knockdown showed extended in vitro life span. Taken together, the present study indicates that IRF3 should be a novel inducer of cell growth inhibition and cellular senescence through activation of p53 tumor suppressor.
Details
- Title: Subtitle
- Interferon regulatory factor 3 activates p53-dependent cell growth inhibition
- Creators
- Tae-Kyung Kim - Korea UniversityJoong-Seob Lee - Korea UniversityJi-Eun Jung - Korea UniversitySe-Yeong Oh - University of SeoulSungwook Kwak - Korea UniversityXun Jin - Korea UniversitySoo-Yeon Lee - Korea UniversityJang-Bo Lee - Korea UniversityYong Gu Chung - Korea UniversityYoung Ki Choi - Chungbuk National UniversitySeungkwon You - Korea UniversityHyunggee Kim - Korea University
- Resource Type
- Journal article
- Publication Details
- Cancer letters, Vol.242(2), pp.215-221
- Publisher
- Elsevier Ireland Ltd
- DOI
- 10.1016/j.canlet.2005.11.003
- PMID
- 16513254
- ISSN
- 0304-3835
- eISSN
- 1872-7980
- Grant note
- DOI: 10.13039/501100013391, name: Ministry of Education and Human Resources Development
- Language
- English
- Date published
- 10/28/2006
- Academic Unit
- Neurosurgery
- Record Identifier
- 9984459624502771
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