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ABSTRACT Enzyme/prodrug approach is one of the actively developing areas for cancer therapy. In an effort to develop more effective enzyme/prodrug systems, cell-permeable cytosine deaminase
was produced by fusing yeast cytosine deaminase (yCD) in frame with RKKRRQRRR domain of HIV-1 Tat which is an efficient delivery peptide of the foreign proteins into cells. The purified
Tat-yCD fusion protein expressed in Escherichia coli was readily transduced into mammalian cells in a time- and dose-dependent manner. A significant level of the transduced Tat-yCD protein
was recovered in the cell and was stable for 24 h as indicated by both results of the enzymatic assay of 5-fluorocytosine (5-FC) conversion to 5-fluorouracil (5-FU) and Western blot
analysis. The cells transduced with Tat-yCD become highly sensitive to the cytotoxicity of 5-FC, while cells treated with yCD are unaffected by 5-FC. In addition, a strong bystander effect
was observed with conditioned media from cells transduced with Tat-yCD added to non-transduced cells. Tat-yCD fusion protein demonstrated here for its ability to transduce into cells and
convert nontoxic prodrug 5-FC to the toxic antimetabolite 5-FU, may be a useful approach for cancer therapy. SIMILAR CONTENT BEING VIEWED BY OTHERS SYNTHETIC LETHAL TARGETING OF
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BY MUTATIONS MODULATING P53 ACTIVITY Article Open access 02 July 2024 ARTICLE PDF AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Division of Life Sciences, College of Natural Sciences, Hallym
University, Chuncheon, 200-702, Korea Hakjoo Lee Authors * Hakjoo Lee View author publications You can also search for this author inPubMed Google Scholar * Jiyoon Ryu View author
publications You can also search for this author inPubMed Google Scholar * Kyung-Ae Kim View author publications You can also search for this author inPubMed Google Scholar * Kil Soo Lee
View author publications You can also search for this author inPubMed Google Scholar * Jae Young Lee View author publications You can also search for this author inPubMed Google Scholar *
Jae-Bong Park View author publications You can also search for this author inPubMed Google Scholar * Jinseu Park View author publications You can also search for this author inPubMed Google
Scholar * Soo Young Choi View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS This is an Open Access article distributed under the
terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and
reproduction in any medium, provided the original work is properly cited. Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Lee, H., Ryu, J., Kim, KA. _et al._ Transduction of
yeast cytosine deaminase mediated by HIV-1 Tat basic domain into tumor cells induces chemosensitivity to 5-fluorocytosine. _Exp Mol Med_ 36, 43–51 (2004). https://doi.org/10.1038/emm.2004.6
Download citation * Published: 01 February 2004 * Issue Date: 01 February 2004 * DOI: https://doi.org/10.1038/emm.2004.6 SHARE THIS ARTICLE Anyone you share the following link with will be
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initiative KEYWORDS * cancer * cytosine deaminase * prodrug * transduction * Tat