Activation of NF-κB by the dsRNA-dependent protein kinase, PKR involves the IκB kinase complex

被引:114
作者
Gil, J
Alcamí, J
Esteban, M
机构
[1] CSIC, Ctr Nacl Biotecnol, Dept Mol & Cellular Biol, Madrid 28049, Spain
[2] Hosp 12 Octubre, Ctr Invest, E-28041 Madrid, Spain
关键词
PKR; NF-kappa B; IKK; dsRNA;
D O I
10.1038/sj.onc.1203448
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Besides its known role as a translational controlling factor, the double stranded RNA-dependent protein kinase (PKR) is a key transcriptional regulator exerting antiviral and antitumoural activities. We have recently described that induction of NF-kappa B by PKR is involved in apoptosis commitment. To define how PKR mediates NF-kappa B activation by dsRNA, we have used two different approaches, one based on expression of PKR by a vaccinia virus (VV) recombinant and the other based on induction of endogenous PKR by poly I:C (pIC) treatment. We found that NF-kappa B complexes induced by PKR are composed primarily of p50-p65 heterodimers and also of c-rel-p50 heterodimers. As described for other stimuli, following pIC treatment, PKR phosphorylates the NF-kappa B inhibitor I kappa B alpha at serine 32 before degradation. Expression by VV recombinants of IKK1 or IKK2 dominant negative mutants together with PKR showed inhibition of PER-induced NF-kappa B activation, as measured both by gel shift and luciferase reporter assays. Immunoprecipitation analysis revealed that PKR interacts with the IKK complex. Our findings demonstrate that physiological function(s) of PKR involve activation of the I kappa B kinase complex.
引用
收藏
页码:1369 / 1378
页数:10
相关论文
共 76 条
[1]   HIGH-LEVELS OF C-REL EXPRESSION ARE ASSOCIATED WITH PROGRAMMED CELL-DEATH IN THE DEVELOPING AVIAN EMBRYO AND IN BONE-MARROW CELLS IN-VITRO [J].
ABBADIE, C ;
KABRUN, N ;
BOUALI, F ;
SMARDOVA, J ;
STEHELIN, D ;
VANDENBUNDER, B ;
ENRIETTO, PJ .
CELL, 1993, 75 (05) :899-912
[2]   A tyrosine-based motif and a casein kinase II phosphorylation site regulate the intracellular trafficking of the varicella-zoster virus glycoprotein I, a protein localized in the trans-Golgi network [J].
Alconada, A ;
Bauer, U ;
Hoflack, B .
EMBO JOURNAL, 1996, 15 (22) :6096-6110
[3]   PHOSPHATIDYLCHOLINE HYDROLYSIS ACTIVATES NF-KAPPA-B AND INCREASES HUMAN-IMMUNODEFICIENCY-VIRUS REPLICATION IN HUMAN MONOCYTES AND T-LYMPHOCYTES [J].
ARENZANASEISDEDOS, F ;
FERNANDEZ, B ;
DOMINGUEZ, I ;
JACQUE, JM ;
THOMAS, D ;
DIAZMECO, MT ;
MOSCAT, J ;
VIRELIZIER, JL .
JOURNAL OF VIROLOGY, 1993, 67 (11) :6596-6604
[4]  
ARENZANASEISDEDOS F, 1995, MOL CELL BIOL, V15, P2689
[5]   NF-kappa B: Ten years after [J].
Baeuerle, PA ;
Baltimore, D .
CELL, 1996, 87 (01) :13-20
[6]   Activation of the dsRNA-dependent protein kinase, PKR, induces apoptosis through FADD-mediated death signaling [J].
Balachandran, S ;
Kim, CN ;
Yeh, WC ;
Mak, TW ;
Bhalla, K ;
Barber, GN .
EMBO JOURNAL, 1998, 17 (23) :6888-6902
[7]   Sequential DNA damage-independent and -dependent activation of NF-κB by UV [J].
Bender, K ;
Göttlicher, M ;
Whiteside, S ;
Rahmsdorf, HJ ;
Herrlich, P .
EMBO JOURNAL, 1998, 17 (17) :5170-5181
[8]   Type I interferon gene expression:: Differential expression of IFN-A genes induced by viruses and double-stranded RNA [J].
Bragança, J ;
Civas, A .
BIOCHIMIE, 1998, 80 (8-9) :673-687
[9]   LIPOPROTEIN METABOLISM IN THE MACROPHAGE - IMPLICATIONS FOR CHOLESTEROL DEPOSITION IN ATHEROSCLEROSIS [J].
BROWN, MS ;
GOLDSTEIN, JL .
ANNUAL REVIEW OF BIOCHEMISTRY, 1983, 52 :223-261
[10]   Activation-dependent transcriptional regulation of the human fas promoter requires NF-κB p50-p65 recruitment [J].
Chan, H ;
Bartos, DP ;
Owen-Schaub, LB .
MOLECULAR AND CELLULAR BIOLOGY, 1999, 19 (03) :2098-2108