Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity

被引:485
作者
Ronco, LV
Karpova, AY
Vidal, M
Howley, PM [1 ]
机构
[1] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Charlestown, MA 02129 USA
[3] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA
关键词
IRF-3; HPV16; transcription; protein-protein interactions; oncoprotein;
D O I
10.1101/gad.12.13.2061
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Interferon regulatory factor-3 (IRF-3) was found to specifically interact with HPV16 E6 in a yeast two-hybrid screen. IRF-3 is activated by the presence of double-stranded RNA or by virus infection to form a stable complex with other transcriptional regulators that bind to the regulatory elements of the IFN beta promoter. We show that IRF-3 is a potent transcriptional activator and demonstrate that HPV16 E6 can inhibit its transactivation function. The expression of HPV16 E6 in primary human keratinocytes inhibits the induction of IFN beta mRNA following Sendai virus infection. The binding of HPV16 E6 to IRF-3 does not result in its ubiquitination or degradation. We propose that the interaction of E6 with IRF-3 and the inhibition of IRF-3's transcriptional activity may provide the virus a means to circumvent the normal antiviral response of an HPV16-infected cell.
引用
收藏
页码:2061 / 2072
页数:12
相关论文
共 69 条
[1]   IDENTIFICATION OF THE HPV-16 E6 PROTEIN FROM TRANSFORMED MOUSE CELLS AND HUMAN CERVICAL-CARCINOMA CELL-LINES [J].
ANDROPHY, EJ ;
HUBBERT, NL ;
SCHILLER, JT ;
LOWY, DR .
EMBO JOURNAL, 1987, 6 (04) :989-992
[2]  
[Anonymous], 1988, Antibodies: A Laboratory Manual
[3]   IDENTIFICATION OF A MEMBER OF THE INTERFERON REGULATORY FACTOR FAMILY THAT BINDS TO THE INTERFERON-STIMULATED RESPONSE ELEMENT AND ACTIVATES EXPRESSION OF INTERFERON-INDUCED GENES [J].
AU, WC ;
MOORE, PA ;
LOWTHER, W ;
JUANG, YT ;
PITHA, PM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (25) :11657-11661
[4]   ENHANCED DEGRADATION OF P53 PROTEIN IN HPV-6 AND BPV-1 E6-IMMORTALIZED HUMAN MAMMARY EPITHELIAL-CELLS [J].
BAND, V ;
DALAL, S ;
DELMOLINO, L ;
ANDROPHY, EJ .
EMBO JOURNAL, 1993, 12 (05) :1847-1852
[5]   Cooperation of Stat2 and p300/CBP in signalling induced by interferon-alpha [J].
Bhattacharya, S ;
Eckner, R ;
Grossman, S ;
Oldread, E ;
Arany, Z ;
DAndrea, A ;
Livingston, DM .
NATURE, 1996, 383 (6598) :344-347
[6]   PREVALENCE OF HUMAN PAPILLOMAVIRUS IN CERVICAL-CANCER - A WORLDWIDE PERSPECTIVE [J].
BOSCH, FX ;
MANOS, MM ;
MUNOZ, N ;
SHERMAN, M ;
JANSEN, AM ;
PETO, J ;
SCHIFFMAN, MH ;
MORENO, V ;
KURMAN, R ;
SHAH, KV ;
ALIHONOU, E ;
BAYO, S ;
MOKHTAR, HC ;
CHICAREON, S ;
DAUDT, A ;
DELOSRIOS, E ;
GHADIRIAN, P ;
KITINYA, JN ;
KOULIBALY, M ;
NGELANGEL, C ;
TINTORE, LMP ;
RIOSDALENZ, JL ;
SARJADI ;
SCHNEIDER, A ;
TAFUR, L ;
TEYSSIE, AR ;
ROLON, PA ;
TORROELLA, M ;
TAPIA, AV ;
WABINGA, HR ;
ZATONSKI, W ;
SYLLA, B ;
VIZCAINO, P ;
MAGNIN, D ;
KALDOR, J ;
GREER, C ;
WHEELER, C .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1995, 87 (11) :796-802
[7]   MOLECULAR-INTERACTIONS BETWEEN INTERFERON CONSENSUS SEQUENCE BINDING-PROTEIN AND MEMBERS OF THE INTERFERON REGULATORY FACTOR FAMILY [J].
BOVOLENTA, C ;
DRIGGERS, PH ;
MARKS, MS ;
MEDIN, JA ;
POLITIS, AD ;
VOGEL, SN ;
LEVY, DE ;
SAKAGUCHI, K ;
APPELLA, E ;
COLIGAN, JE ;
OZATO, K .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (11) :5046-5050
[8]   MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I ANTIGENS AND THE CONTROL OF VIRAL-INFECTIONS BY NATURAL-KILLER-CELLS [J].
BRUTKIEWICZ, RR ;
WELSH, RM .
JOURNAL OF VIROLOGY, 1995, 69 (07) :3967-3971
[9]   INTERACTION OF PAPILLOMAVIRUS E6 ONCOPROTEINS WITH A PUTATIVE CALCIUM-BINDING PROTEIN [J].
CHEN, JJ ;
REID, CE ;
BAND, V ;
ANDROPHY, EJ .
SCIENCE, 1995, 269 (5223) :529-531
[10]   DEGRADATION OF P53 CAN BE TARGETED BY HPV E6 SEQUENCES DISTINCT FROM THOSE REQUIRED FOR P53 BINDING AND TRANSACTIVATION [J].
CROOK, T ;
TIDY, JA ;
VOUSDEN, KH .
CELL, 1991, 67 (03) :547-556