Abstract
Phage ΦC31 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 ΦC31 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 ΦC31 integrase-mediated integration. A possible effect of interaction between ΦC31 integrase and TTRAP was highlighted by the fact that ΦC31 integrase inhibited the NFκB activation mediated by IL-1 in a dose-dependent manner. Because low dose of ΦC31 integrase can mediate considerable recombination events, we suggest that low dose of ΦC31 integrase be used when this integrase is applied in human cells.
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Acknowledgments
We are very grateful to Michele P. Calos for providing the pCMV-Int plasmid. We also thank Shen Q. for her technical support. This work was supported by the National Basic Research Program of China (973, 2004CB518803), State High Technology Development Program (863, 2007aa021002 and 2006aa02Z161) and Nature Science Fund (30771236).
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Wang, By., Xu, Gl., Zhou, Ch. et al. ΦC31 integrase interacts with TTRAP and inhibits NFκB activation. Mol Biol Rep 37, 2809–2816 (2010). https://doi.org/10.1007/s11033-009-9829-3
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DOI: https://doi.org/10.1007/s11033-009-9829-3