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Mol. Cells 2004; 17(2): 353-359

Published online January 1, 1970

© The Korean Society for Molecular and Cellular Biology

Intracellular Delivery of p53 Fused to the Basic Domain of HIV-1 Tat

Jiyoon Ryu, Hak Joo Lee, Kyeong-Ae Kim, Jae Yong Lee, Kil Soo Lee, Jinseu Park, Soo Young Choi

Abstract

p53 is a potent tumor suppressor inactivated in many cancers. In this study, the membrane permeability of the HIV-1 Tat basic domain was exploited to introduce functional p53 into cancer cells. We expressed and purified a p53 fusion protein with the HIV-1 Tat basic domain at its N terminus (Tat-p53), and examined its transduction profile and biological activity in cancer cells. Tat-p53 was efficiently delivered to both the cytoplasm and nucleus of cells, and was transcriptionally active, as judged by the level of p21/WAF1 protein and of p21 promoter activity. Transduction of cells with Tat-p53 resulted in apoptotic cell death in both p53 positive and negative human tumor cell lines. These results suggest that Tat-p53 could be useful in cancer therapy.

Keywords Apoptosis; Cancer Therapy; Tat; Transduction; Tumor Suppressor

Article

Research Article

Mol. Cells 2004; 17(2): 353-359

Published online April 30, 2004

Copyright © The Korean Society for Molecular and Cellular Biology.

Intracellular Delivery of p53 Fused to the Basic Domain of HIV-1 Tat

Jiyoon Ryu, Hak Joo Lee, Kyeong-Ae Kim, Jae Yong Lee, Kil Soo Lee, Jinseu Park, Soo Young Choi

Abstract

p53 is a potent tumor suppressor inactivated in many cancers. In this study, the membrane permeability of the HIV-1 Tat basic domain was exploited to introduce functional p53 into cancer cells. We expressed and purified a p53 fusion protein with the HIV-1 Tat basic domain at its N terminus (Tat-p53), and examined its transduction profile and biological activity in cancer cells. Tat-p53 was efficiently delivered to both the cytoplasm and nucleus of cells, and was transcriptionally active, as judged by the level of p21/WAF1 protein and of p21 promoter activity. Transduction of cells with Tat-p53 resulted in apoptotic cell death in both p53 positive and negative human tumor cell lines. These results suggest that Tat-p53 could be useful in cancer therapy.

Keywords: Apoptosis, Cancer Therapy, Tat, Transduction, Tumor Suppressor

Mol. Cells
Jun 30, 2023 Vol.46 No.6, pp. 329~398
COVER PICTURE
The cellular proteostasis network is adaptively modulated upon cellular stress, thereby protecting cells from proteostasis collapse. Heat shock induces the translocation of misfolded proteins and the chaperone protein HSP70 into nucleolus, where nuclear protein quality control primarily occurs. Nuclear RNA export factor 1 (green), nucleolar protein fibrillarin (red), and nuclei (blue) were visualized in NIH3T3 cells under basal (left) and heat shock (right) conditions (Park et al., pp. 374-386).

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