Interaction with PI3-kinase contributes to the cytotoxic activity of apoptin.

Abstract:

: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.

journal_name

Oncogene

journal_title

Oncogene

authors

Maddika S,Wiechec E,Ande SR,Poon IK,Fischer U,Wesselborg S,Jans DA,Schulze-Osthoff K,Los M

doi

10.1038/sj.onc.1210958

subject

Has Abstract

pub_date

2008-05-08 00:00:00

pages

3060-5

issue

21

eissn

0950-9232

issn

1476-5594

pii

1210958

journal_volume

27

pub_type

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