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Interaction with PI3-kinase contributes to the cytotoxic activity of Apoptin
Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada; Manitoba Institute of Cell Biology, CancerCare Manitoba, University of Manitoba, Winnipeg, Manitoba, Canada; Department of Therapeutic Radiology, Yale School of Medicine, New Haven, USA.
Manitoba Institute of Cell Biology, CancerCare Manitoba; Department of Human Genetics, University of Aarhus, Aarhus, Denmark,.
Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada; Manitoba Institute of Cell Biology, CancerCare Manitoba, University of Manitoba, Winnipeg, Manitoba, Canada.
Nuclear Signaling Laboratory, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
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2008 (Engelska)Ingår i: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 27, s. 3060-3065Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Apoptin, a small protein from the chicken anemia virus, has attracted attention because of its specificity in killing tumor cells. Localization of apoptin in the nucleus of tumor cells has been shown to be vital for proapoptotic activity, however, targeted expression of apoptin in the nucleus of normal cells does not harm the cells, indicating that nuclear localization of apoptin is insufficient for its cytotoxicity. Here, we demonstrate for the first time that apoptin interacts with the SH3 domain of p85, the regulatory subunit of phosphoinositide 3-kinase (PI3-K), through its proline-rich region. Apoptin derivatives devoid of this proline-rich region do not interact with p85, are unable to activate PI3-K, and show impaired apoptosis induction. Moreover, apoptin mutants containing the proline-rich domain are sufficient to elevate PI3-K activity and to induce apoptosis in cancer cells. Downregulation of p85 leads to nuclear exclusion of apoptin and impairs cell death induction, indicating that interaction with the p85 PI3-K subunit essentially contributes to the cytotoxic activity of apoptin.

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Nature Publishing Group, 2008. Vol. 27, s. 3060-3065
Nyckelord [en]
anticancer drugs, apoptin, apoptosis, PI3-kinase
Nationell ämneskategori
Cancer och onkologi Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci) Biokemi och molekylärbiologi Cellbiologi
Identifikatorer
URN: urn:nbn:se:liu:diva-86928DOI: 10.1038/sj.onc.1210958ISI: 000255681700013PubMedID: 18059340OAI: oai:DiVA.org:liu-86928DiVA, id: diva2:583315
Tillgänglig från: 2013-01-07 Skapad: 2013-01-07 Senast uppdaterad: 2017-12-06

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Wiechec, EmiliaLos, Marek Jan

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Cancer och onkologiMedicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)Biokemi och molekylärbiologiCellbiologi

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