PhiC31 integrase interacts with TTRAP and inhibits NFkappaB activation.
Phage PhiC31 integrase-mediated gene delivery is believed to be safer than using retroviral vectors since the protein confines its insertion of the target gene to a limited number of sites in mammalian genomes. To evaluate its safety in human cells, it is important to understand the interactions between this integrase and cellular proteins. Here we show that PhiC31 integrase interacts with TTRAP as presented by yeast two-hybrid and co-immunoprecipitation assays. Reducing the expression of endogenous TTRAP can increase the efficiency of PhiC31 integrase-mediated integration. A possible effect of interaction between PhiC31 integrase and TTRAP was highlighted by the fact that PhiC31 integrase inhibited the NFkappaB activation mediated by IL-1 in a dose-dependent manner. Because low dose of PhiC31 integrase can mediate considerable recombination events, we suggest that low dose of PhiC31 integrase be used when this integrase is applied in human cells.
Wang
Bing-yin
BY
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China.
Xu
Guan-lan
GL
Zhou
Cai-hong
CH
Tian
Ling
L
Xue
Jing-lun
JL
Chen
Jin-zhong
JZ
Jia
William
W
D001435:Bacteriophages / Q000187:drug effects / Q000201:enzymology*; D006367:HeLa Cells; D006801:Humans; D019426:Integrases / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011995:Recombination, Genetic / Q000187:drug effects; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000378:metabolism*; D016662:Virus Integration / Q000187:drug effects
D007375:Interleukin-1; D016328:NF-kappa B; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D019426:Integrases