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 beta-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 induc...Continue Reading
References
May 31, 1990·Nature·C B HarleyC W Greider
Sep 26, 1995·Proceedings of the National Academy of Sciences of the United States of America·G P DimriO Pereira-Smith
May 12, 2000·Science·E OdaN Tanaka
Aug 31, 2000·Cell·C J Sherr, R A DePinho
Oct 18, 2000·The Journal of Biological Chemistry·M J ServantJ Hiscott
Feb 28, 2002·Proceedings of the National Academy of Sciences of the United States of America·Alla Y KarpovaPeter M Howley
Aug 3, 2002·Nature Reviews. Cancer·Karen H Vousden, Xin Lu
Oct 2, 2002·Immunity·Sean DoyleGenhong Cheng
Feb 4, 2003·Nature Reviews. Cancer·Patrick Chène
Feb 13, 2003·The Journal of Biological Chemistry·Tae Young KimTae Kook Kim
Jul 23, 2003·Nature·Akinori TakaokaTadatsugu Taniguchi
Dec 1, 1961·Experimental Cell Research·L HAYFLICK, P S MOORHEAD
Feb 19, 2004·Journal of the National Cancer Institute·Carmela GurrieriPier Paolo Pandolfi
Apr 23, 2004·Nature·David DornanVishva M Dixit
Mar 1, 2005·Cell·Judith Campisi
Citations
Jan 23, 2009·Cell Research·Jean-François ClémentMarc J Servant
Jan 10, 2009·Nature Reviews. Cancer·Thomas Kuilman, Daniel S Peeper
Jun 15, 2007·The Journal of Experimental Medicine·Zachary J RobertsStefanie N Vogel
Sep 12, 2007·PLoS Genetics·Oleg GarifulinVictor Boyartchuk
Mar 7, 2014·Cardiovascular Research·Shu-Min ZhangHongliang Li
Jun 19, 2012·Trends in Cell Biology·Karol SzczepanekAndrew C Larner
Dec 17, 2008·Mechanisms of Ageing and Development·Kwang Seok KimJae-Ryong Kim
May 18, 2010·International Journal of Cancer. Journal International Du Cancer·Yu ZhangBaiqu Huang
Dec 26, 2013·Cancer Letters·Tyler C MooreThomas M Petro
Dec 6, 2014·Current Rheumatology Reports·Sonsoles Piera-Velazquez, Sergio A Jimenez
May 21, 2013·Innate Immunity·Jiin-Tarng WangMei-Ru Chen
Jan 26, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Rui LiQing-Duo Guo
Apr 14, 2017·Physiology·Yaxing Zhang, Hongliang Li
May 8, 2015·Cell Death & Disease·S KumarH Kumar
Jul 10, 2019·Frontiers in Cellular Neuroscience·Xi ZhangJian Ye
May 23, 2020·Nature Communications·Bo YuShusheng Wang
Apr 15, 2020·Experimental & Molecular Medicine·Abdul BasitJae-Ho Lee
Jun 2, 2017·Scientific Reports·Lu-Lu WangGuo-Ping Zhou
Dec 25, 2019·Nature Immunology·Maria Esperanza Rodriguez-RuizLorenzo Galluzzi
Dec 7, 2007·Cancer Research·Tae-Kyung KimHyunggee Kim
May 22, 2021·Osteoarthritis and Cartilage·Qiang GuoYaosen Wu