Play all audios:
ABSTRACT Apoptin has been described to induce apoptosis in various human cancer cell lines, but not in normal cells, thus making it an interesting candidate for the development of novel
therapeutic strategies. Apoptin was generated and cloned into several mammalian expression vectors. Transfection or microinjection of apoptin cDNA resulted in its expression, initially in
the cytoplasm with a filamentous pattern. Subsequently, apoptin entered the nucleus and efficiently induced apoptosis in several cancer cell lines. Nuclear localization was shown to be
required for induction of apoptosis. Apoptin expression level was found to be an important determinant of the efficiency of induction of apoptosis. Surprisingly, expression of apoptin or
GFP-apoptin cDNA induced apoptosis in some normal cells. When fused to the HIV-TAT protein transduction domain and delivered as a protein, TAT-apoptin was transduced efficiently (>90%)
into normal and tumour cells. However, TAT-apoptin remained in the cytoplasm and did not kill normal 6689 and 1BR3 fibroblasts. In contrast TAT-apoptin migrated from the cytoplasm to the
nucleus of Saos-2 and HSC-3 cancer cells resulting in apoptosis after 24 h. This study shows that apoptin is a powerful apoptosis-inducing protein with a potential for cancer therapy. Access
through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal
Receive 50 print issues and online access $259.00 per year only $5.18 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may
be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support
SIMILAR CONTENT BEING VIEWED BY OTHERS ENHANCED ONCOLYTIC ADENOVIRAL PRODUCTION BY DOWNREGULATION OF DEATH-DOMAIN ASSOCIATED PROTEIN AND OVEREXPRESSION OF PRECURSOR TERMINAL PROTEIN Article
Open access 13 January 2021 CASPASE INHIBITION IMPROVES VIABILITY AND EFFICIENCY OF LIPOSOMAL TRANSFECTION Article Open access 10 December 2023 A SMALL-MOLECULE ARTS MIMETIC PROMOTES
APOPTOSIS THROUGH DEGRADATION OF BOTH XIAP AND BCL-2 Article Open access 25 June 2020 REFERENCES * Becker-Hapak M, McAllister SS and Dowdy SF . (2001). _Methods_, 24, 247–256. * Cohen JJ .
(1993). _Immunol Today_, 14, 126–130. * Danen-Van Oorschot AA, Fischer DF, Grimbergen JM, Klein B, Zhuang S, Falkenburg JH, Backendorf C, Quax PH, Van der Eb AJ and Noteborn MH . (1997).
_Proc Natl Acad Sci USA_, 94, 5843–5847. * Danen-van Oorschot AA, van Der Eb AJ and Noteborn MH . (2000). _J Virol_, 74, 7072–7078. * Danen-Van Oorschot AA, Zhang Y, Erkeland SJ, Fischer DF,
van der Eb AJ and Noteborn MH . (1999). _Leukemia_, 13 (Suppl 1), S75–S77. * Danen-Van Oorschot AA, Zhang YH, Leliveld SR, Rohn JL, Seelen MC, Bolk MW, Van Zon A, Erkeland SJ, Abrahams JP,
Mumberg D and Noteborn MH . (2003). _J Biol Chem_, 278, 27729–27736. * Flinterman M, Gaken J, Farzaneh F and Tavassoli M . (2003). _Oncogene_, 22, 1965–1977. * Ford KG, Souberbielle BE,
Darling D and Farzaneh F . (2001). _Gene Ther_, 8, 1–4. * Gius DR, Ezhevsky SA, Becker-Hapak M, Nagahara H, Wei MC and Dowdy SF . (1999). _Cancer Res_, 59, 2577–2580. * Holme TC . (1990).
_Eur J Surg Oncol_, 16, 161–169. * Janicke RU, Sprengart ML, Wati MR and Porter AG . (1998). _J Biol Chem_, 273, 9357–9360. * Mann DA and Frankel AD . (1991). _Embo J_, 10, 1733–1739. *
Meehan BM, Todd D, Creelan JL, Earle JA, Hoey EM and McNulty MS . (1992). _Arch Virol_, 124, 301–319. * Nagahara H, Vocero-Akbani AM, Snyder EL, Ho A, Latham DG, Lissy NA, Becker-Hapak M,
Ezhevsky SA and Dowdy SF . (1998). _Nat Med_, 4, 1449–1452. * Noteborn MH, de Boer GF, van Roozelaar DJ, Karreman C, Kranenburg O, Vos JG, Jeurissen SH, Hoeben RC, Zantema A and Koch G et
al. (1991). _J Virol_, 65, 3131–3139. * Noteborn MH, Todd D, Verschueren CA, de Gauw HW, Curran WL, Veldkamp S, Douglas AJ, McNulty MS, van der EA and Koch G . (1994). _J Virol_, 68,
346–351. * Noteborn MH, Zhang YH and van der Eb AJ . (1998). _Mutat Res_, 400, 447–455. * Rohn JL, Zhang YH, Aalbers RI, Otto N, Den Hertog J, Henriquez NV, Van De Velde CJ, Kuppen PJ,
Mumberg D, Donner P and Noteborn MH . (2002). _J Biol Chem_, 277, 50820–50827. * Schwarze SR, Ho A, Vocero-Akbani A and Dowdy SF . (1999). _Science_, 285, 1569–1572. * Schwarze SR, Hruska KA
and Dowdy SF . (2000). _Trends Cell Biol_, 10, 290–295. * Siegel RM, Martin DA, Zheng L, Ng SY, Bertin J, Cohen J and Lenardo MJ . (1998). _J Cell Biol_, 141, 1243–1253. * Vives E, Brodin P
and Lebleu B . (1997). _J Biol Chem_, 272, 16010–16017. * Vocero-Akbani AM, Heyden NV, Lissy NA, Ratner L and Dowdy SF . (1999). _Nat Med_, 5, 29–33. * Weber CH and Vincenz C . (2001).
_Trends Biochem Sci_, 26, 475–481. * Zhang YH, Abrahams PJ, van der Eb AJ and Noteborn MH . (1999). _Cancer Res_, 59, 3010–3015. * Zhuang SM, Landegent JE, Verschueren CA, Falkenburg JH, van
Ormondt H, van der Eb AJ and Noteborn MH . (1995a). _Leukemia_, 9 (Suppl 1), S118–S120. * Zhuang SM, Shvarts A, Jochemsen AG, van Oorschot AA, van der Eb AJ and Noteborn MH . (1995b).
_Carcinogenesis_, 16, 2939–2944. * Zhuang SM, Shvarts A, van Ormondt H, Jochemsen AG, van der Eb AJ and Noteborn MH . (1995c). _Cancer Res_, 55, 486–489. Download references ACKNOWLEDGEMENTS
We are grateful to Dr Daniel Todd (Department of Agriculture and Rural Development for Northern Ireland, the Queen's University of Belfast) for providing pCAA-3 and anti-VP3 monoclonal
antibody and for very useful discussions. We are grateful to Dr Steven F Dowdy (Howard Hughes Medical Institute, Department of Pathology, Washington University School of Medicine) for
providing pTAT-HA and pTAT-HA-GFP, to Dr Alan Lehmann (MRC Cell Mutation Unit, University of Sussex) for 1BR3 and 1BR3N cells, to Dr Martin Dyer (MRC Toxicology Unit, University of
Leicester) for pGFP-Bcl10 and Dr Richard Siegel (NIAID NIH Bethesda) for pFADD-GFP. This study was supported by a grant from the BBSRC (47/GTH12530). AUTHOR INFORMATION AUTHORS AND
AFFILIATIONS * Department of Oral Medicine and Pathology, Head and Neck Oncology Group, The Rayne Institute, Guy's, King's and St Thomas' School of Medicine and Dentistry,
London, UK Lars Guelen, Michelle Meyers & Mahvash Tavassoli * CRC Centre for Cell and Molecular Biology, Chester Beatty Laboratories, Institute of Cancer Research, London, UK Hugh
Paterson * Department of Molecular Medicine, The Rayne Institute, Guy's, King's and St Thomas' School of Medicine and Dentistry, London, UK Joop Gäken & Farzin Farzaneh
Authors * Lars Guelen View author publications You can also search for this author inPubMed Google Scholar * Hugh Paterson View author publications You can also search for this author
inPubMed Google Scholar * Joop Gäken View author publications You can also search for this author inPubMed Google Scholar * Michelle Meyers View author publications You can also search for
this author inPubMed Google Scholar * Farzin Farzaneh View author publications You can also search for this author inPubMed Google Scholar * Mahvash Tavassoli View author publications You
can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Mahvash Tavassoli. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS
ARTICLE Guelen, L., Paterson, H., Gäken, J. _et al._ TAT-apoptin is efficiently delivered and induces apoptosis in cancer cells. _Oncogene_ 23, 1153–1165 (2004).
https://doi.org/10.1038/sj.onc.1207224 Download citation * Received: 23 July 2003 * Revised: 10 September 2003 * Accepted: 22 September 2003 * Published: 22 December 2003 * Issue Date: 05
February 2004 * DOI: https://doi.org/10.1038/sj.onc.1207224 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a
shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * apoptin * CAV * apoptosis *
TAT-PTD * protein delivery * death effector