Journal article
Direct Transcriptional Activation of Promyelocytic Leukemia Protein by IFN Regulatory Factor 3 Induces the p53-Dependent Growth Inhibition of Cancer Cells
Cancer research (Chicago, Ill.), Vol.67(23), pp.11133-11140
12/01/2007
DOI: 10.1158/0008-5472.CAN-07-1342
PMID: 18056437
Abstract
IFN 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, and is also involved in p53-dependent inhibition of cell growth. Although functional activation of IRF3 by viral infection is relatively well documented, the biological role and regulatory mechanism underlying cell growth inhibition by IRF3 are poorly understood. Here, we show a novel regulatory pathway connecting IRF3-promyelocytic leukemia protein (PML)-p53 in primary and cancer cell lines. Overexpression of IRF3 induces p53-dependent cell growth inhibition in cancer cell lines with normal p53 activity. In addition, doxycycline-induced expression of IRF3 in U87MG cells inhibits tumor growth in nude mice in vivo. IRF3 is found to increase expression of PML by a direct transcriptional activation as determined by PML-promoter-luciferase and chromatin immunoprecipitation assays. When PML is depleted by RNA interference–mediated knockdown, IRF3 fails to increase p53 acetylation and its transcriptional activity. Taken together, the results of the present study indicate that direct transcriptional activation of PML by IRF3 results in the p53-dependent growth inhibition of normal and cancer cells in vitro and in vivo, which is suggestive of a novel regulatory network between the innate immune response and tumor suppression
Details
- Title: Subtitle
- Direct Transcriptional Activation of Promyelocytic Leukemia Protein by IFN Regulatory Factor 3 Induces the p53-Dependent Growth Inhibition of Cancer Cells
- Creators
- Tae-Kyung Kim - Korea UniversityJoong-Seob Lee - The Laboratory of Cell Growth and Function Regulation, Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Korea, Republic ofJang-Bo Lee - Department of Neurosurgery, School of Medicine, Korea University, Korea, Republic ofRonald A Depinho - Harvard University PressLynda Chin - Harvard University PressHyunggee Kim - The Laboratory of Cell Growth and Function Regulation, Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Korea, Republic ofSe-Yeong OH - The Laboratory of Cell Growth and Function Regulation, Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Korea, Republic ofXUN Jin - Seoul National UniversityYun-Jaie Choi - Seoul National UniversityTae-Hoon Lee - Chonnam National University HospitalEUN HO Lee - Chungbuk National UniversityYoung-Ki Choi - Chungbuk National UniversitySeungkwon You - The Laboratory of Cell Growth and Function Regulation, Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Korea, Republic ofYONG GU Chung - Department of Neurosurgery, School of Medicine, Korea University, Korea, Republic of
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.67(23), pp.11133-11140
- DOI
- 10.1158/0008-5472.CAN-07-1342
- PMID
- 18056437
- NLM abbreviation
- Cancer Res
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Publisher
- American Association for Cancer Research
- Language
- English
- Date published
- 12/01/2007
- Academic Unit
- Neurosurgery
- Record Identifier
- 9984460339002771
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