title: PhiC31 integrase interacts with TTRAP and inhibits NFkappaB activation.
abstract: 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.
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Bing-yin
authors.initials: BY
authors.lastname: Wang
authors.forename: Guan-lan
authors.initials: GL
authors.lastname: Xu
authors.forename: Cai-hong
authors.initials: CH
authors.lastname: Zhou
authors.forename: Ling
authors.initials: L
authors.lastname: Tian
authors.forename: Jing-lun
authors.initials: JL
authors.lastname: Xue
authors.forename: Jin-zhong
authors.initials: JZ
authors.lastname: Chen
authors.forename: William
authors.initials: W
authors.lastname: Jia
mesh_terms: 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
chemical_list: D007375:Interleukin-1; D016328:NF-kappa B; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D019426:Integrases